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Maternal vitamin status contributes to clinical spontaneous abortion, but the role of B-vitamin and homocysteine status in subclinical early pregnancy loss is unknown. Three-hundred sixty-four textile workers from Anqing, China, who conceived at least once during prospective observation (1996-1998), provided daily urine specimens for up to 1 year, and urinary human chorionic gonadatropin was assayed to detect conception and early pregnancy loss. Homocysteine, folate, and vitamins B(6) and B(12) were measured in preconception plasma. Relative to women in the lowest quartile of vitamin B(6), those in the third and fourth quartiles had higher adjusted proportional hazard ratios of conception (hazard ratio (HR) = 2.2, 95% confidence interval (CI): 1.3, 3.4; HR = 1.6, 95% CI: 1.1, 2.3, respectively), and the adjusted odds ratio for early pregnancy loss in conceptive cycles was lower in the fourth quartile (odds ratio = 0.5, 95% CI: 0.3, 1.0). Women with sufficient vitamin B(6) had a higher adjusted hazard ratio of conception (HR = 1.4, 95% CI: 1.1, 1.9) and a lower adjusted odds ratio of early pregnancy loss in conceptive cycles (odds ratio = 0.7, 95% CI: 0.4, 1.1) than did women with vitamin B(6) deficiency. Poor vitamin B(6) status appears to decrease the probability of conception and to contribute to the risk of early pregnancy loss in this population. [ABSTRACT FROM AUTHOR]

Background: Cardio-cerebrovascular disease is an important public health challenge worldwide, and its complex etiology has not been elucidated fully. The study investigated the relationship between two common polymorphisms, C677T and A1298C in the methylenetetrahydrofolate reductase (MTHFR) gene, baseline lipids and the lipid-lowering efficacy of simvastatin in a Chinese hyperlipidemic population., Methods: All participants were recruited from Anhui, China. By the extreme sampling method, we selected subjects with a low response (n=108) and high response (n=106) based on their adjusted lipid-lowering response to simvastatin administrated for 8 consecutive weeks. Both MTHFR C677T and A1298C loci were genotyped by the MALDI-TOF MS platform. Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured at baseline and after 8 weeks of oral 20 mg/d tablets of simvastatin., Results: Patients with the 677TT genotype had significantly higher baseline TC, HDL-C, and change in HDL-C (ΔHDL-C) levels after treatment than those with 677CC+CT genotypes (β = 0.207, P = 0.045; β = 0.182, P = 0.026; and β = 0.16, P = 0.002, respectively). Patients with 1298AC+CC genotypes had significantly higher baseline LDL-C and change in LDL-C (ΔLDL-C) levels (β = 0.276, P =0.043; β = 0.359, P = 0.025, respectively) than those with 1298AA genotype. We found statistical interactions between the two SNPs in association with baseline HDL-C (P for interaction = 0.034), TC (P for interaction = 0.069), and TG (P for interaction = 0.034). Baseline TC (P = 0.027) and HDL-C (P = 0.046) and change in HDL-C (P = 0.019) were different among those with the MTHFR A-T haplotype compared with A-C., Conclusion: Our major findings suggest that both MTHFR C677T and A1298C polymorphisms could be important genetic determinants of lipid traits and drug efficacy of simvastatin. This will contribute to a better understanding of strategies for personalized medication in Chinese patients with dyslipidemia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Hypertension is an important public health challenge worldwide. Epigenetic studies are providing novel insight into the underlying mechanisms of hypertension. We investigated the effect of DNA methylation in ATP-binding cassette transporter 1 (ABCA1) gene on blood pressure levels in a Chinese hyperlipidemic population. We randomly selected 211 individuals with hyperlipidemia who had not received any lipid-lowering treatment at baseline from our previous statin pharmacogenetics study (n = 734). DNA methylation loci at the ABCA1 gene were measured by MethylTarget, a next generation bisulfite sequencing-based multiple targeted cytosine-guanine dinucleotide methylation analysis method. Mean DNA methylation level was used in statistical analysis. In all subjects, higher mean ABCA1_B methylation was positively associated with systolic blood pressure (SBP) (β = 8.27, P = 0.008; β = 8.78, P = 0.005) and explained 2.7% and 5.8% of SBP variation before and after adjustment for lipids, respectively. We further divided all patients into three groups based on the tertile of body mass index (BMI) distribution. In the middle tertile of BMI, there was a significantly positive relationship between mean ABCA1_A methylation and SBP (β = 0.89, P = 0.003) and DBP (β = 0.32, P = 0.030). Mean ABCA1_A methylation explained 11.0% of SBP variation and 5.3% of DBP variation, respectively. Furthermore, mean ABCA1_A methylation (β = 0.79; P = 0.007) together with age and gender explained up to 24.1% of SBP variation. Our study provides new evidence that the ABCA1 DNA methylation profile is associated with blood pressure levels, which highlights that DNA methylation might be a significant molecular mechanism involved in the pathophysiological process of hypertension., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Importance: Gestational exposure to particulate matter (PM) air pollution may increase the risk of childhood obesity, but the impact of reducing air pollution during pregnancy on obesity-related outcomes in childhood has not been examined., Objective: To assess the impact of reducing gestational PM exposure on body mass index (BMI) at two years of age., Methods: In this single-blind, parallel group randomized controlled trial in Ulaanbaatar Mongolia, we randomly assigned 540 pregnant women to receive 1-2 portable high efficiency particulate air (HEPA) filter air cleaners or no air cleaners. We measured height and weight when children were a mean age of 23.8 months. Our primary outcome was age- and sex-specific BMI z-score based on the World Health Organization 2007 Growth Charts. Secondary outcomes included age- and sex-specific weight z score, overweight/obesity (defined as BMI z-score > 2.00), and catch-up growth (defined using various cut-offs to identify children with relatively low birth weight for sex and gestational age and relatively high age- and sex-specific weight in childhood). We imputed missing outcome data using multiple imputation with chained equations and our primary analysis was by intention to treat (ITT). We estimated intervention effects on continuous and binary outcomes using linear and logistic regression, respectively., Results: After excluding known miscarriages, still births, and neonatal deaths our analysis included 480 children (235 control and 245 intervention). The mean (SD) child BMI z score was 0.79 (1.0); 9.8% of children were overweight or obese. The mean BMI z score of children who were randomly assigned to the intervention group was 0.16-units lower (95% CI: -0.35, 0.04) than children in the control group. The intervention was also associated with reductions in overweight/obesity (odds ratio = 0.59; 95% CI: 0.31, 1.12). Catch-up growth occurred less frequently in the intervention group, but effect estimates varied depending on the specific definition of catch-up growth and confidence intervals consistently spanned no effect., Conclusions: We found that the use of portable air cleaners during pregnancy was associated with improvements in obesity-related outcomes, although some effect estimates lacked precision. Reducing PM exposure during pregnancy may lead to improvements in cardiometabolic health in childhood., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: We investigated the effect of ABCG1 gene DNA methylation in the lipid-lowering efficacy of simvastatin. Materials & methods: An extreme sampling approach was used to select 211 individuals from the top and bottom 15% of adjusted lipid-lowering response residuals to simvastatin after eight consecutive weeks. DNA methylation was measured before treatment by the MethylTarget bisulfite sequencing method. Results: ABCG1_A DNA methylations were negatively associated with baseline high-density lipoprotein cholesterol (HDL-C) and the change in HDL-C after treatment. ABCG1_C methylations were also related to the change in triglyceride and HDL-C. Moreover, mean ABCG1_A and ABCG1_C methylations explain 7.2% of the ΔTC (total cholesterol) and 17.5% of the ΔHDL-C level variability, respectively. Conclusion: DNA methylations at the ABCG1 gene play significant inhibitory effects in the lipid-lowering therapy of simvastatin.

Background: Gestational cadmium exposure may impair fetal growth. Coal smoke has largely been unexplored as a source of cadmium exposure. We investigated the relationship between gestational cadmium exposure and fetal growth, and assessed coal smoke as a potential source of airborne cadmium, among non-smoking pregnant women in Ulaanbaatar, Mongolia, where coal combustion in home heating stoves is a major source of outdoor and indoor air pollution., Methods: This observational study was nested within the Ulaanbaatar Gestation and Air Pollution Research (UGAAR) study, a randomized controlled trial of portable high efficiency particulate air (HEPA) filter air cleaner use during pregnancy, fetal growth, and early childhood development. We measured third trimester blood cadmium concentrations in 374 out of 465 participants who had a live birth. We used multiple linear and logistic regression to assess the relationships between log 2 -transformed maternal blood cadmium concentrations and birth weight, length, head circumference, ponderal index, low birth weight, small for gestational age, and preterm birth in crude and adjusted models. We also evaluated the relationships between log 2 -transformed blood cadmium concentrations and the density of coal-burning stoves within 5000 m of each participant's apartment as a proxy of coal smoke emissions from home heating stoves., Results: The median (25th,75th percentile) blood cadmium concentration was 0.20 (0.15, 0.29) μg/L. A doubling of blood cadmium was associated with a 95 g (95% CI: 34, 155 g) reduction in birth weight in adjusted models. An interquartile range increase in coal stove density (from 3.4 to 4.9 gers/hectare) surrounding participants' apartments was associated with a 12.2% (95% CI: 0.3, 25.6%) increase in blood cadmium concentrations., Conclusions: Gestational cadmium exposure was associated with reduced birth weight. In settings where coal is a widely used fuel, cadmium may play a role in the putative association between air pollution and impaired fetal growth., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social communication and repetitive or stereotypic behaviours. In utero exposure to environmental chemicals, such as polychlorinated biphenyls (PCBs), may play a role in the etiology of ASD. We examined the relation between plasma PCB concentrations measured during pregnancy and autistic behaviours in a subset of children aged 3⁻4 years old in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pregnancy and birth cohort of 546 mother-infant pairs from Canada (enrolled: 2008⁻2011). We quantified the concentrations of 6 PCB congeners that were detected in >40% of plasma samples collected during the 1st trimester. At age 3⁻4 years, caregivers completed the Social Responsiveness Scale-2 (SRS), a valid and reliable measure of children's reciprocal social and repetitive behaviours and restricted interests. We examined SRS scores as both a continuous and binary outcome, and we calculated Bayesian predictive odds ratios for more autistic behaviours based on a latent variable model for SRS scores >60. We found no evidence of an association between plasma PCB concentrations and autistic behaviour. However, we found small and imprecise increases in the mean SRS score and odds of more autistic behaviour for the highest category of plasma PCB concentrations compared with the lowest category; for instance, an average increase of 1.4 (95%PCI: -0.4, 3.2) in the mean SRS (exposure contrast highest versus lowest PCB category) for PCB138 translated to an odds ratio of 1.8 (95%PCI: 1.0, 2.9). Our findings illustrate the importance of measuring associations between PCBs and autistic behaviour on both continuous and binary scales.

Background: Indoor and outdoor fine particulate matter (PM 2.5 ) are both leading risk factors for death and disease, but making indoor measurements is often infeasible for large study populations., Methods: We developed models to predict indoor PM 2.5 concentrations for pregnant women who were part of a randomized controlled trial of portable air cleaners in Ulaanbaatar, Mongolia. We used multiple linear regression (MLR) and random forest regression (RFR) to model indoor PM 2.5 concentrations with 447 independent 7-day PM 2.5 measurements and 87 potential predictor variables obtained from outdoor monitoring data, questionnaires, home assessments, and geographic data sets. We also developed blended models that combined the MLR and RFR approaches. All models were evaluated in a 10-fold cross-validation., Results: The predictors in the MLR model were season, outdoor PM 2.5 concentration, the number of air cleaners deployed, and the density of gers (traditional felt-lined yurts) surrounding the apartments. MLR and RFR had similar performance in cross-validation (R 2  = 50.2%, R 2  = 48.9% respectively). The blended MLR model that included RFR predictions had the best performance (cross validation R 2  = 81.5%). Intervention status alone explained only 6.0% of the variation in indoor PM 2.5 concentrations., Conclusions: We predicted a moderate amount of variation in indoor PM 2.5 concentrations using easily obtained predictor variables and the models explained substantially more variation than intervention status alone. While RFR shows promise for modelling indoor concentrations, our results highlight the importance of out-of-sample validation when evaluating model performance. We also demonstrate the improved performance of blended MLR/RFR models in predicting indoor air pollution., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Fine particulate matter (PM 2.5 ) exposure may impair fetal growth., Aims/objectives: Our aim was to assess the effect of portable high efficiency particulate air (HEPA) filter air cleaner use during pregnancy on fetal growth., Methods: The Ulaanbaatar Gestation and Air Pollution Research (UGAAR) study is a single-blind randomized controlled trial conducted in Ulaanbaatar, Mongolia. Non-smoking pregnant women recruited at ≤18 weeks gestation were randomized to an intervention (1-2 air cleaners in homes from early pregnancy until childbirth) or control (no air cleaners) group. Participants were not blinded to their intervention status. Demographic, health, and birth outcome data were obtained via questionnaires and clinic records. We used unadjusted linear and logistic regression and time-to-event analysis to evaluate the intervention. Our primary outcome was birth weight. Secondary outcomes were gestational age-adjusted birth weight, birth length, head circumference, gestational age at birth, and small for gestational age. The study is registered at ClinicalTrials.gov (NCT01741051)., Results: We recruited 540 participants (272 control and 268 intervention) from January 9, 2014 to May 1, 2015. There were 465 live births and 28 losses to follow up. We previously reported a 29% (95% CI: 21, 37%) reduction in indoor PM 2.5 concentrations with portable HEPA filter air cleaner use. The median (25th, 75th percentile) birth weights for control and intervention participants were 3450 g (3150, 3800 g) and 3550 g (3200, 3800 g), respectively (p = 0.34). The intervention was not associated with birth weight (18 g; 95% CI: -84, 120 g), but in a pre-specified subgroup analysis of 429 term births the intervention was associated with an 85 g (95% CI: 3, 167 g) increase in mean birth weight., Conclusions: HEPA filter air cleaner use in a high pollution setting was associated with greater birth weight only among babies born at term., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Our goal was to examine the associations of the 388A>G and 521T>C polymorphisms in the solute carrier organic anion transporter 1B1 (SLCO1B1) gene with hepatic function, baseline lipid levels, and the lipid-lowering efficiency of simvastatin. We recruited 542 patients with hyperlipidemia. The 388A>G and 521T>C polymorphisms were genotyped. Serum alanine aminotransferase (ALT) and aspartate transaminase (AST), Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured before and after an oral 20-mg dose of simvastatin. Individuals with the 388AA genotype had higher ALT and AST levels than those with the 388AG or 388GG genotypes (P = .037 and P = .002, respectively). Individuals with both the 388AA and the 521TT genotypes had the highest levels of ALT and AST (P = .001 and P = .001, respectively). Moreover, we divided all patients into normal and abnormal subgroups based on elevated ALT and AST values (≥ 40 U/L), participants in the abnormal subgroup had a higher frequency of the 388A/521T haplotype and a lower frequency of the 388G/521T haplotype compared to those in the normal subgroup.  In addition, compared to 388G allele and 521C allele carriers, individuals with the 388G allele and 521TT genotype carriers had greater TC and LDL-C reduction in response to simvastatin after 4 weeks of treatment. Our conclusion suggests that the interaction between the SLCO1B1 388A>G and 521T>C polymorphisms could be an important genetic determinant of hepatic function and the therapeutic efficiency of simvastatin in Chinese patients with hyperlipidemia.

This study was conducted to explore interactions in the association of the kininogen (KNG1) Ile197Met polymorphism and gender with plasma concentrations of irbesartan in Chinese patients with essential hypertension. A total of 1100 subjects with essential hypertension received a daily oral dose of 150 mg irbesartan for twenty-eight consecutive days. High-performance liquid chromatography-fluorescence (HPLC) was used to detect plasma irbesartan concentrations on day 28. The KNG1 Ile197Met gene polymorphism was determined using high-throughput TaqMan technology. The frequency distribution of KNG1 Ile197Met genotype conformed to the Hardy-Weinberg equilibrium. After 28 days of treatment, patients with the GG genotype had significantly lower irbesartan concentrations (P = 0.033) compared to homozygous TT genotype carriers. After stratifying by gender, male G allele carriers had significantly lower irbesartan concentrations (GG, P = 0.015; TG, P = 0.015, respectively) relative to TT genotype after adjusting for age, region, body mass index (BMI), smoking, and alcohol consumption. However, there was no significant difference in female subjects. A further test for a multiplicative interaction between the KNG1 Ile197Met polymorphism and gender in association with ln-plasma irbesartan concentrations in a multiple linear regression model was also significant (P for interaction = 0.033). This is the first study to suggest that gender may influence the association of the Ile197Met variant of KNG1 with ln-plasma irbesartan concentration. This finding may indicate that the interaction of gender and the KNG1 Ile197Met gene polymorphism can influence plasma trough irbesartan concentrations, which may contribute to a better development of personalized hypertensive treatment in Chinese patients.

We conducted a cross-sectional study to investigate the effects of the adenosine triphosphate-binding cassette transporter 1 (ABCA1) I883M and lipoprotein lipase (LPL) HindIII polymorphisms on lipid levels in patients with hyperlipidemia. A total of 533 patients were enrolled. Serum lipid parameters were determined by an automatic biochemistry analyzer. Genotyping of the ABCA1 I883M and LPL HindIII was carried out using the polymerase chain reaction-restriction fragment length polymorphism technique. Multiple linear regression analysis was used to estimate the associations between serum lipid levels and the genetic polymorphisms. The frequency distribution of the ABCA1 I883M and LPL HindIII polymorphisms did not deviate from Hardy-Weinberg equilibrium. The major finding of our regression analysis showed that neither the ABCA1 I883M nor the LPL HindIII polymorphism was associated with baseline serum lipid levels in the total population. However, among patients with elevated alanine aminotransferase (ALT) levels (ALT ≥ 40 U/L), carriers of the M allele of the ABCA1 gene had lower levels of high-density lipoprotein cholesterol (HDL-C) and higher levels of low-density lipoprotein cholesterol (LDL-C) after adjusting for age, sex, smoking status, alcohol consumption, education level, occupation, and work intensity ( P < .05 for both). A test on interaction terms between the ABCA1 I833M polymorphism and ALT on HDL-C and LDL-C levels also remained significant ( P = .001 and P = .014, respectively). Our data suggest that there are significant interactive effects between ABCA1 I883M and ALT levels on HDL-C and LDL-C levels. However, the LPL HindIII polymorphism did not influence lipid levels.

Background: Portable HEPA filter air cleaners can reduce indoor fine particulate matter (PM 2.5 ), but their use has not been adequately evaluated in high pollution settings. We assessed air cleaner effectiveness in reducing indoor residential PM 2.5 and second hand smoke (SHS) exposures among non-smoking pregnant women in Ulaanbaatar, Mongolia., Methods: We randomized 540 participants to an intervention group receiving 1 or 2 HEPA filter air cleaners or a control group receiving no air cleaners. We followed 259 intervention and 253 control participants to the end of pregnancy. We measured one-week indoor residential PM 2.5 concentrations in early (~11weeks gestation) and late (~31weeks gestation) pregnancy and collected outdoor PM 2.5 data from centrally-located government monitors. We assessed blood cadmium in late pregnancy. Hair nicotine was quantified in a subset (n=125) to evaluate blood cadmium as a biomarker of SHS exposure. We evaluated air cleaner effectiveness using mixed effects and multiple linear regression models and used stratified models and interaction terms to evaluate potential modifiers of effectiveness., Results: The overall geometric mean (GM) one-week outdoor PM 2.5 concentration was 47.9μg/m 3 (95% CI: 44.6, 51.6μg/m 3 ), with highest concentrations in winter (118.0μg/m 3 ; 110.4, 126.2μg/m 3 ). One-week indoor and outdoor PM 2.5 concentrations were correlated (r=0.69). Indoor PM 2.5 concentrations were 29% (21, 37%) lower in intervention versus control apartments, with GMs of 17.3μg/m 3 (15.8, 18.8μg/m 3 ) and 24.5μg/m 3 (22.2, 27.0μg/m 3 ), respectively. Air cleaner effectiveness was greater when air cleaners were first deployed (40%; 31, 48%) than after approximately five months of use (15%; 0, 27%). Blood cadmium concentrations were 14% (4, 23%) lower among intervention participants, likely due to reduced SHS exposure., Conclusions: Portable HEPA filter air cleaners can lower indoor PM 2.5 concentrations and SHS exposures in highly polluted settings., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To confirm the association between baseline blood pressure (BP) levels and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism in patients with essential hypertension., Methods: A total of 347 patients were enrolled from the Dongzhi community in Anhui Province, China. The C677T polymorphism of the MTHFR gene was detected using high-throughput TaqMan allelic discrimination assay. Baseline BP was measured using a standardized mercury-gravity monometer., Results: In the whole sample, the frequency of the MTHFR C677T genotypes CC, CT, and TT were 38.6%, 48.1%, and 13.3%, respectively. In a recessive model (CC+CT versus TT genotypes), baseline diastolic blood pressure (DBP) was significantly higher in patients with the TT genotype compared to those with the CT or CC genotypes (P= 0.013). We also divided all patients into three groups based on the tertiles of the baseline BP distribution. Compared to subjects in the lowest tertile of DBP, the adjusted odds of having the TT genotype among subjects in the highest tertile was 2.6 (95% CI: 1.1 to 6.2). However, no significant associations were observed between baseline systolic blood pressure (SBP) and the MTHFR C677T polymorphism., Conclusions: The MTHFR gene polymorphism could be an important genetic determinant of baseline DBP levels in Chinese essential hypertensive patients.

We investigated the associations of LEP G2548A and LEPR Q223R polymorphisms with statin-induced creatine kinase (CK) elevation among Chinese patients with hyperlipidemia. A total of587 enrolled individuals were treated with 20 mg/d oral simvastatin for 8 consecutive weeks. Genotyping of LEP G2548A and LEPR Q223R were conducted using PCR-RFLP. Multiple regression analyses showed that, in the Dongzhi region only, patients carrying the LEP AA genotype had a significantly greater increase in CK levels compared to those carrying the AG+GG genotypes after four weeks ( P = 0.004) and eight weeks ( P < 0.001) consecutive simvastatin treatment. Patients were further divided into three groups based on the tertiles of the CK distribution. Compared to subjects in the lowest tertile of CK elevation, the adjusted relative odds of having the AG+GG genotypes among subjects in the highest tertile was 0.5 (95% CI, 0.3 to 0.7) and 0.4 (95% CI, 0.2 to 0.6) after the fourth and eighth weeks, respectively. The interaction terms between the Beijing or Dongzhi region and the LEP GA+AA genotypes were marginally significant for CK elevation at the fourth week ( P = 0.057) and significant for CK elevation at the eighth week ( P = 0.002). The adverse effect of the LEP G2548A polymorphism on increasing CK levels may be dependent on the environmental milieu. It suggests that lifestyle interventions might offset the side effects of simvastatin therapy among those with genetic susceptibility. Further research is needed to identify specific individual-level factors for clinical practice that modify the effect of genotype., Competing Interests: CONFLICTS OF INTEREST The authors declare no competing financial interests.

We evaluated 2,4-dichlorophenoxyacetic acid (2,4-D) exposure in four municipalities with and without cosmetic pesticide bylaws in British Columbia, Canada. We recruited a child (aged 1.5-5 years) and adult from 10 households in each city, who provided urine samples in May and June, 2009. No households had used pesticides for 7 days prior to sample collection. We quantified urinary 2,4-D using LC/MS/MS. Quantities of 2,4-D in urine were similar across cities and below biomonitoring equivalents corresponding to references doses in the United State of America and Canada. When adult's and children's urines were analyzed together in linear mixed-effects regression models, natural log urinary 2,4-D was significantly associated with having a diet of ⩾50% organic food (β=-0.6 (0.3) μg/l, P=0.05). Without natural log transformation, median concentration of urinary 2,4-D among those who ate ⩾50% organic food (n=12) was 1.4 μg/l versus 1.5 μg/l for others (n=59). Lack of a significant association (two-sided alpha=0.05) between pesticide bylaws and urinary 2,4-D might reflect small sample size, lack of recent acute exposure, or that 2,4-D exposure is primarily influenced by sources of exposure not addressed through bylaws. Food might be a route of exposure to 2,4-D, consistent with other studies. Future research will require larger sample sizes for sufficient statistical power.

Objectives: To investigate whether LEP G2548A and LEPR Q223R polymorphisms influence serum lipid levels and whether the 2 polymorphisms affect the efficacy of simvastatin treatment in Chinese patients with primary hyperlipidemia., Methods: We used an extreme sampling approach by selecting 212 individuals from the top and bottom 15% of adjusted lipid-lowering response residuals to simvastatin (n = 106 in each group of good or bad response) from a total of 734 samples with primary hyperlipidemia. They were treated with simvastatin orally 20 mg/d. Fasting serum lipids were measured at baseline and after 4 and 8 weeks of treatment. Genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism., Results: More patients in the good response group (27%) had LEPR Q223R than in the bad response group (16%, P = .046). Secondary stratified analyses showed that patients carrying the RR genotype of the LEPR Q223R gene had significantly higher high-density lipoprotein cholesterol levels than those with the QR genotype at baseline ( P = .034) among good responders. After 29 consecutive days of treatment with simvastatin, patients carrying the RR genotype had a significantly larger decrease in triglycerides (change: -0.74 ± 0.92, P = .036) and total cholesterol levels (change: -1.77 ± 0.68, P = .023) compared with those carrying QR genotype among bad responders. After Bonferroni correction, the results were not statistically significant., Conclusion: LEPR Q223R polymorphism, but not LEP G2548A, could modulate the efficacy of simvastatin in Chinese patients with primary hyperlipidemia.

We aimed to examine the cross-sectional associations of plasma total homocysteine (tHcy) concentrations and methylenetetrahydrofolate reductase ( MTHFR) C677T genotype with dyslipidemia. A total of 231 patients with mild-to-moderate essential hypertension were enrolled from the Huoqiu and Yuexi communities in Anhui Province, China. Plasma tHcy levels were measured by high-performance liquid chromatography. Genotyping was performed by TaqMan allelic discrimination technique. Compared with MTHFR 677 CC + CT genotype carriers, TT genotype carriers had higher odds of hypercholesterolemia (adjusted odds ratio [OR] [95% confidence interval (CI)]: 2.7 [1.4-5.2]; P = .004) and higher odds of abnormal low-density lipoprotein cholesterol (adjusted OR [95% CI]: 2.3 [1.1-4.8]; P = .030). The individuals with the TT genotype had higher concentrations of log(tHcy) than those with the 677 CC + CT genotype (adjusted β [standard error]: .2 [0.03]; P < .001). Patients with tHcy ≥ 10 μmol/L had significantly higher odds of hypercholesterolemia (adjusted OR [95% CI]: 2.4 [1.2-4.7]; P = .010). Furthermore, patients with both the TT genotype and the tHcy ≥ 10 μmol/L had the highest odds of hypercholesterolemia (adjusted OR [95% CI]: 4.1 [1.8-9.4]; P = .001) and low-density lipoprotein cholesterol (adjusted OR [95% CI]: 2.4 [1.0-6.0]; P = .064). This study suggests that both tHcy and the MTHFR C677T gene polymorphism may be important determinants of the incidence of dyslipidemia in Chinese patients with essential hypertension. Further studies are needed to confirm the role of tHcy and the MTHFR C677T mutation in the development of dyslipidemia in a larger sample.

Background: Hyperhomocysteinemia is a risk factor for cardiovascular disease. To date, limited prospective studies have examined the joint effects of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, hyperhomocysteinemia and conventional vascular risk factors on risk of stroke and stroke death., Methods: A total of 39 165 subjects from nine communities within Anqing, Anhui Province, China were prospectively followed from March 1995 to April 2005, with an average follow-up period of 6.2 years. None of the subjects had any history of vascular events at baseline. At follow-up, 251 incident stroke cases were identified. Using a nested, case-control study design, this analysis includes 106 cases with complete MTHFR C677T genotyping data and plasma samples. We selected 106 controls without vascular events matched for age, sex, community and years of plasma storage. Plasma total homocysteine (tHcy) level was measured by high-performance liquid chromatography., Results: Hypertension was independently associated with incident stroke and stroke death after adjusting for important covariates including plasma log-transformed Hcy level. Relative to non-carriers of the MTHFR 677TT genotype with no hypertension, the adjusted odds ratio (95% confidence interval) of stroke and stroke death among hypertensive carriers of the MTHFR 677TT genotype was 10.6 (3.2 to 34.8), 5.8 (1.6 to 21.3), respectively. After excluding subjects with plasma Hcy above 20 μmol/L, the relative odds for stroke, but not for stroke death, was more significantly pronounced (OR = 24.1, 95% CI: 2.3 to 246.1) among subjects with moderate plasma Hcy levels. However, there was no significant interactive effect between hypertensive status and the MTHFR C677T variant on the odds of the two outcomes as estimated by interaction models., Conclusions: Our major findings suggest that joint effects of the MTHFR C677T polymorphism and hypertension are consistent in predicting a significantly high risk of stroke. In addition for moderate plasma levels of Hcy, the predicted effects on the risk for the primary end point of stroke were more pronounced. These results may help to modify current approaches to vascular disease prevention in Chinese hypertensive patients.

The aim of the present study was to examine the association between peripheral differential leukocyte counts and dyslipidemia in a Chinese hypertensive population. A total of 10,866 patients with hypertension were enrolled for a comprehensive assessment of cardiovascular risk factors using data from the China Stroke Primary Prevention Trial. Plasma lipid levels and total leukocyte, neutrophil, and lymphocyte counts were determined according to standard methods. Peripheral differential leukocyte counts were consistently and positively associated with serum total cholesterol (TC), LDL cholesterol (LDL-C), and TG levels (all P < 0.001 for trend), while inversely associated with HDL cholesterol levels (P < 0.05 for trend). In subsequent analyses where serum lipids were dichotomized (dyslipidemia/normolipidemia), we found that patients in the highest quartile of total leukocyte count (≥7.6 × 10 9 cells/l) had 1.64 times the risk of high TG [95% confidence interval (CI): 1.46, 1.85], 1.34 times the risk of high TC (95% CI: 1.20, 1.50), and 1.24 times the risk of high LDL-C (95% CI: 1.12, 1.39) compared with their counterparts in the lowest quartile of total leukocyte count. Similar patterns were also observed with neutrophils and lymphocytes. In summary, these findings indicate that elevated differential leukocyte counts are directly associated with serum lipid levels and increased odds of dyslipidemia., (Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.)

Background: Perfluoroalkyl acids (PFASs) are suspected thyroid toxicants, but results from epidemiological studies are inconsistent., Objectives: We examined associations between serum PFASs and thyroid hormones (THs) in a representative, cross-sectional sample of U.S. adults. We hypothesized that people with high thyroid peroxidase antibodies and low iodine would be more susceptible to PFAS-induced thyroid disruption., Methods: Our sample included 1,525 adults (≥ 18 years) from the 2007-2008 NHANES study with available serum PFASs and THs. We examined associations between four serum PFASs [perfluorohexane sulfonate (PFHxS), perfluorononanoate (PFNA), perfluorooctanoate (PFOA), and perfluorooctane sulfonate (PFOS)], and serum THs [free triiodothyronine (fT3), free thyroxine (fT4), fT3/fT4, thyroid-stimulating hormone (TSH), total T3 (TT3), and total T4 (TT4)] using multivariable linear regression. We stratified subjects into four groups by two indicators of thyroid "stress": thyroid peroxidase antibody (TPOAb ≥ 9 IU/mL) and iodine status (< 100 μg/L urine)., Results: Of 1,525 participants, 400 (26%) had low iodine only (T0I1), 87 (6%) had high TPOAb only (T1I0), and 26 (2%) had both high TPOAb and low iodine (T1I1). In general, associations were similar among participants in the groups with neither (T0I0) or only one thyroid stressor (T0I1 or T1I0), suggesting that PFAS-TH associations were not modified by high TPOAb or low iodine alone. However, PFHxS and PFOS were negatively associated (p < 0.05) with fT4, and all four PFASs were positively associated (p < 0.05) with fT3, fT3/fT4, TSH, and TT3 in the group with joint exposure to high TPOAb and low iodine (T1I1)., Conclusions: We found evidence of PFAS-associated thyroid disruption in a subset of U.S. adults with high TPOAb (a marker of autoimmune hypothyroidism) and low iodine status, who may represent a vulnerable subgroup. However, the small sample size, cross-sectional design, and possibility of reverse causation are limitations of this work., Citation: Webster GM, Rauch SA, Ste Marie N, Mattman A, Lanphear BP, Venners SA. 2016. Cross-sectional associations of serum perfluoroalkyl acids and thyroid hormones in U.S. adults: variation according to TPOAb and iodine status (NHANES 2007-2008). Environ Health Perspect 124:935-942; http://dx.doi.org/10.1289/ehp.1409589.

Objective: This study was designed to detect the association of the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene polymorphism with antihypertensive therapeutic response to irbesartan in a large-scale Chinese hypertensive population., Methods: A total of 1,099 patients with essential hypertension were enrolled to receive a daily dose of 150 mg irbesartan for 27 days. Pretreatment baseline blood pressure (BP) and posttreatment BP on the 28th day were measured. Plasma irbesartan concentrations were measured by high-performance liquid chromatography-fluorescence. The KCNJ11 I337V gene polymorphism was determined using high-throughput TaqMan technology., Results: The HapMap data in the Han Chinese population showed that the I337V was used as a representative for 4 common functional polymorphisms. Our results showed that the association of antihypertensive response to irbesartan and the KCNJ11 genetic variant in the total sample was not significant. However, in nonsmokers, relative to the GG genotype, subjects with the homozygous AA genotype had a significantly higher therapeutic response to irbesartan (adjusted beta ± SE: 4.7±1.9 mm Hg, P = 0.015). In smokers, the subjects with the homozygous AA genotype had a significantly lower therapeutic response to irbesartan (adjusted beta ± SE: -5.6±2.5 mm Hg, P = 0.026). A multivariate linear regression model confirmed that there was a significant interactive effect between the KCNJ11 gene and smoking on irbesartan treatment (interaction P = 0.001)., Conclusion: The interactive effect of smoking status and the KCNJ11 genotype may influence the antihypertensive effects of irbesartan, which indicates a consideration for future individualized antihypertensive drug treatment., (© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To investigate the effect of benazepril on plasma homocysteine (Hcy) levels and to analyze the correlation between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and changes in Hcy levels in response to benazepril., Methods: A total of 231 patients with mild to moderate essential hypertension were enrolled, and benazepril was orally administered at a dose of 10 mg/d for 2 weeks. Plasma Hcy levels were measured by high-performance liquid chromatography at baseline and after 2 weeks of treatment. Genotyping of the MTHFR C677T polymorphism was performed by TaqMan probe technique., Results: There was no significant change in Hcy level after benazepril treatment for 2 weeks (P = .97). However, stratified by baseline Hcy levels, the patients with baseline Hcy <10 μmol/L had a significant increase in plasma Hcy levels (P = .003). The results from the multivariable linear regression analysis demonstrated a significant correlation between baseline Hcy levels and the changes in Hcy levels found in both the unadjusted (P = .002) and the adjusted model (P = .004). Strikingly, we found no significant effect modification by the MTHFR C677T polymorphism on the Hcy changes after benazepril treatment. There were also no statistically significant interactions of gene and environment factors (ie, gene smoking and drinking) on the changes in Hcy levels after benazepril treatment., Conclusion: Benazepril may cause an increase in plasma Hcy levels among patients with hypertension with low baseline Hcy levels, while effect modification by MTHFR C677T genotypes on the changes in Hcy levels in response to benazepril was not significant among patients with essential hypertension., (© The Author(s) 2015.)

Background: Persons with mental illness are over-represented in prison populations around the world. They are more vulnerable to arrest and more likely to experience repeated encounters with the criminal justice system. Whether criminal justice involvement, in and of itself, is associated with higher mortality, particularly among offenders with mental illness, is unknown., Methods: The authors conducted a mediation analysis of mortality rates in a cohort of 79,088 offenders from British Columbia using administrative records spanning 2001-2010, where the mediating variable was the individual-level rate of criminal sentencing., Results: During 339,506 person-years of follow-up, there were 1841 deaths. The diagnosis of mental illness had no direct association with higher mortality after adjustment for confounders (HR=0.98, 95% CI 0.86 to 1.06). However, mental illness had an indirect association with mortality that was mediated through more frequent criminal justice involvement (HR=1.02, 95% CI 1.01 to 1.04)., Conclusions: These findings support the hypothesis that offenders with mental illness experience higher mortality that is mediated by higher rates of criminal justice contact. The results of our study indicate that criminal justice diversion programmes are further warranted because they may contribute to the prevention of mortality among offenders with mental illness., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background. Since most tuberculosis (TB) cases in immigrants to British Columbia (BC), Canada, develop from latent TB infection (LTBI), treating immigrants for LTBI can contribute to the eradication of TB. However, adherence to LTBI treatment is a challenge that is influenced by knowledge and perceptions. This research explores Chinese immigrants' knowledge and perceptions towards LTBI in Greater Vancouver. Methods. This mixed methods study included a cross-sectional patient survey at BC's Provincial TB clinics and two focus group discussions (FGDs) with Chinese immigrants. Data from FGDs were coded and analyzed in Simplified Chinese. Codes, themes, and selected quotes were then translated into English. Results. The survey identified a mean basic knowledge score: 40.0% (95% CI: 38.3%, 41.7%). FGDs confirmed that Chinese immigrants' knowledge of LTBI was low, and they confused it with TB disease to the extent of experiencing LTBI associated stigma. Participants also expressed difficulties navigating the health system which impeded testing and treatment of LTBI. Online videos were the preferred format for receiving health information. Conclusion. We identified striking gaps in knowledge surrounding an LTBI diagnosis. Concerns of stigma may influence acceptance and adherence of LTBI treatment in Chinese immigrants. Integrating these findings into routine health care is recommended.

Background: Although preconception 1,1,1-trichloro-2,2,bis(p-chlorophenyl)ethane (DDT) exposure and B-vitamin deficiencies have each been shown to negatively affect human reproductive outcomes, little is known about their joint effect., Objective: We sought to examine whether B-vitamin sufficiency protects against adverse effects of DDT on clinical pregnancy (CP) and subclinical early pregnancy loss (EPL)., Design: We measured preconception concentrations of plasma B vitamins (vitamin B-6, vitamin B-12, and folate) and serum total DDT [sum of p,p' and o,p' isomers of DDT and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] in 291 nulligravid women from Anhui, China, who were studied in 1996-1998. The women were followed prospectively from the time they stopped contraception until CP (gestational age ≥42 d) or 12 mo (whichever occurred first). EPL was identified by using daily urinary human chorionic gonadotropin. The women were categorized according to B-vitamin status (deficiency compared with sufficiency) and DDT concentration (high compared with low)., Results: Of 291 study women, a total of 385 conceptions (31% of which ended in EPL) and 265 CPs occurred. Compared with women with adequate B-vitamins and low DDT, incidence rates of CP were reduced in women with B-vitamin deficiency and a high DDT concentration (P < 0.05 for all). Most notably, in women with sufficient vitamin B-12, DDT was not associated with the incidence of CP; in contrast, in women with vitamin B-12 deficiency, high DDT was associated with a lower incidence of CP (HR: 0.44; 95% CI: 0.23, 0.84); and the test for interaction was significant (P < 0.05). The odds of EPL decreased by 45% (95% CI: 21%, 62%) for each interquartile distance increase in folate in women with high DDT concentrations, and the test for interaction was significant (P = 0.006)., Conclusions: Our results provide suggestive evidence that vitamin B-12 and folate sufficiency may help protect against adverse reproductive effects of DDT exposure. Additional studies are needed to confirm our findings., (© 2014 American Society for Nutrition.)

Background: Early-life exposure to bisphenol A (BPA) may increase childhood obesity risk, but few prospective epidemiological studies have investigated this relationship., Objective: We sought to determine whether early-life exposure to BPA was associated with increased body mass index (BMI) at 2-5 years of age in 297 mother-child pairs from Cincinnati, Ohio (HOME Study)., Methods: Urinary BPA concentrations were measured in samples collected from pregnant women during the second and third trimesters and their children at 1 and 2 years of age. BMI z-scores were calculated from weight/height measures conducted annually from 2 through 5 years of age. We used linear mixed models to estimate BMI differences or trajectories with increasing creatinine-normalized BPA concentrations., Results: After confounder adjustment, each 10-fold increase in prenatal (β = -0.1; 95% CI: -0.5, 0.3) or early-childhood (β = -0.2; 95% CI: -0.6, 0.1) BPA concentrations was associated with a modest and nonsignificant reduction in child BMI. These inverse associations were suggestively stronger in girls than in boys [prenatal effect measure modification (EMM) p-value = 0.30, early-childhood EMM p-value = 0.05], but sex-specific associations were imprecise. Children in the highest early-childhood BPA tercile had lower BMI at 2 years (difference = -0.3; 95% CI: -0.6, 0.0) and larger increases in their BMI slope from 2 through 5 years (BMI increase per year = 0.12; 95% CI: 0.07, 0.18) than children in the lowest tercile (BMI increase per year = 0.07; 95% CI: 0.01, 0.13). All associations were attenuated without creatinine normalization., Conclusions: Prenatal and early-childhood BPA exposures were not associated with increased BMI at 2-5 years of age, but higher early-childhood BPA exposures were associated with accelerated growth during this period.

Background: Associations between perfluoroalkyl acids (PFASs) and human thyroid hormone levels remain unclear, especially during early pregnancy when small changes in maternal thyroid hormones can affect fetal brain development., Objectives: To examine associations between maternal serum PFAS levels and maternal thyroid hormone levels in the early 2nd trimester of pregnancy., Methods: Participants were euthyroid pregnant women (n=152) enrolled in the Chemicals, Health and Pregnancy (CHirP) study based in Vancouver, Canada. Associations between maternal serum PFASs, including perfluorohexanesulfonate (PFHxS), perfluorononanoate (PFNA), perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) and repeated measures of maternal thyroid hormones, including free thyroxine (fT4), total thyroxine (TT4) and thyroid stimulating home (TSH) were examined using mixed effects linear models. Associations were considered in all women, then separately in women with high (≥ 9 IU/mL) vs normal (<9 IU/mL) levels of thyroid peroxidase antibody (TPOAb), a marker of autoimmune hypothyroidism (Hashimoto's disease)., Results: Median PFAS concentrations (ng/mL) in maternal sera were 1.0 (PFHxS), 0.6 (PFNA), 1.7 (PFOA) and 4.8 (PFOS). PFASs were not associated with fT4, TT4 or TSH among women with normal TPOAb. However, among the 9% of women with high TPOAb (n=14), interquartile range (IQR) increases of PFASs were associated with a 46-69% increase in maternal TSH (95% CIs ranging from 8% to 123%) (PFNA, PFOA and PFOS only), and with a 3% to 7% decrease in maternal fT4 (95% CIs ranging from -18% to 5%) (all 4 PFASs). PFNA was also associated with higher maternal TSH in the whole sample., Conclusions: PFASs were positively associated with TSH, and weakly negatively associated with fT4 in the subset of pregnant women with high TPOAb, which occurs in 6-10% of pregnancies. PFASs may exacerbate the already high TSH and low fT4 levels in these women during early pregnancy, which is a critical time of thyroid hormone-mediated fetal brain development. The clinical significance of these findings is not clear. We propose a "multiple hit hypothesis" to explain these findings; this hypothesis deserves evaluation in larger, more representative study samples., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To examine the effects of the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene polymorphisms and their interactions with environmental factors on serum lipid levels., Methods: We investigated totally 340 patients with essential hypertension, from Dongzhi community, Anhui, China. High-throughput TaqMan allelic discrimination assay was used for the genotyping of MTHFR C677T (Ala222Val), MTHFR A1298C (Glu429Ala), MTRR A66G (Ile22Met), and MTRR His595Tyr., Results: Compared with the MTRR 66AA genotype carriers, the GG genotype carriers had lower serum total cholesterol (TC) levels (adjusted β ± standard error [SE]: -0.5 ± 0.2 mmol/L; P = .003) and low-density lipoprotein cholesterol (LDL-C) levels (adjusted β ± SE: -0.4 ± 0.2 mmol/L; P = .005). Their false discovery rate (FDR)-adjusted P values were 0.056 and 0.056, respectively. We further found that there was a statistically significant interaction between 677TT genotype and sex in their associations with LDL levels (P interaction = .020), and significant interaction between 677TT genotype and smoking on LDL levels (P interaction = .036). A similar pattern of interaction was found between 66GG and drinking on levels of TC (P interaction = .034) and LDL (P interaction = .020). However, there were no significant interactions observed after FDR adjustment., Conclusion: Both MTHFR and MTRR gene polymorphisms could be important genetic determinants of serum lipid levels in Chinese patients with hypertension. These findings need to be replicated in a larger sample.

Objective: We investigate the effect of simvastatin on plasma homocysteine (Hcy) levels and whether genetic factor affects the effect of simvastatin., Methods: A total of 338 patients with hyperlipidemia were enrolled. Simvastatin was orally administered at a dose of 20 mg/day for 8 weeks. Plasma Hcy levels were measured by high-performance liquid chromatography at baseline and after 8 weeks of treatment. Genotyping of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism was performed by TaqMan probe technique., Results: Serum total Hcy levels were positively correlated with serum creatinine (r = 0.332, P < 0.001). Among total subjects, simvastatin treatment resulted in a significant reduction in serum Hcy levels after 8 weeks (-0.37 ± 2.21 μmol/L, P = 0.003), and this effect was dependent on the initial levels of serum Hcy. The individuals with 677TT genotype had a significantly higher baseline Hcy level and a greater change in Hcy levels. After stratification by body mass index (BMI), we observed a significant increase in Hcy levels among the TT genotype group in adjusted model (beta±SE: 2.64 ± 0.84 μmol/L; P = 0.002) among patients with BMI ≥ 25 (kg/m(2) )., Conclusions: Simvastatin can cause a marked decrease in plasma Hcy levels. MTHFR C677T genetic variant contributes to simvastatin's effects among Chinese subjects with primary hyperlipidemia., (© 2012 John Wiley & Sons Ltd.)

Background: The major aim of this study was to investigate whether maternal risk factors associated with socioeconomic status and small for gestational age (SGA) might be viable targets of interventions to reduce differential risk of SGA by socioeconomic status (socioeconomic SGA inequality) in the metropolitan area of Vancouver, Canada., Methods: This study included 59,039 live, singleton births in the Vancouver Census Metropolitan Area (Vancouver) from January 1, 2006 to September 17, 2009. To identify an indicator of socioeconomic SGA inequality, we used hierarchical logistic regression to model SGA by area-level variables from the Canadian census. We then modelled SGA by area-level average income plus established maternal risk factors for SGA and calculated population attributable SGA risk percentages (PAR%) for each variable. Associations of maternal risk factors for SGA with average income were investigated to identify those that might contribute to SGA inequality. Finally, we estimated crude reductions in the percentage and absolute differences in SGA risks between highest and lowest average income quintiles that would result if interventions on maternal risk factors successfully equalized them across income levels or eliminated them altogether., Results: Average income produced the most linear and statistically significant indicator of socioeconomic SGA inequality with 8.9% prevalence of SGA in the lowest income quintile compared to 5.6% in the highest. The adjusted PAR% of SGA for variables were: bottom four quintiles of height (51%), first birth (32%), bottom four quintiles of average income (14%), oligohydramnios (7%), underweight or hypertension, (6% each), smoking (3%) and placental disorder (1%). Shorter height, underweight and smoking during pregnancy had higher prevalence in lower income groups. Crude models assuming equalization of risk factors across income levels or elimination altogether indicated little potential change in relative socioeconomic SGA inequality and reduction in absolute SGA inequality for shorter height only., Conclusions: Our findings regarding maternal height may indicate trans-generational aetiology for socioeconomic SGA inequalities and/or that adult height influences social mobility. Conditions affecting foetal and childhood growth might be viable targets to reduce absolute socioeconomic SGA inequality in future generations, but more research is needed to determine whether such an approach is appropriate.

Objectives: To evaluate the effect of maternal administration of antenatal steroids (ANS) on cord blood cytokine levels at birth in preterm infants., Methods: Cord blood cytokine concentrations were measured for pro-inflammatory cytokines (IL-1β, IL-6, and IL-8); anti-inflammatory cytokines (IL-4, IL-10 and TGF-β); and neurotrophic cytokines (BDNF, NT-3, and NT-4) in two hundred preterm infants. Data were analyzed using multivariable linear regression to model the independent and joint effects of ANS and inflammation on mean log cord blood cytokine concentrations adjusted for gestational age and Apgar scores., Results: Exposure to ANS had no significant effect on the cord blood concentrations of cytokines measured in this study. All three pro-inflammatory cytokine levels and levels of IL-10 were significantly increased and cord blood levels of TGF-β and NT-3 were significantly decreased in infants with placental inflammation., Conclusion: Although exposure to ANS did not have any significant effect on cord blood levels of cytokines, there was a trend toward the attenuation of inflammatory response and higher levels of neurotrophic cytokines in infants born to mothers with placental inflammation and exposure to ANS compared to infants born to mothers with placental inflammation and no ANS exposure., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

A glycosylated polypeptide, β-defensin 126 (DEFB126), derived from the epididymis and adsorbed onto the sperm surface, has been implicated in immunoprotection and efficient movement of sperm in mucosal fluids of the female reproductive tract. Here, we report a sequence variant in DEFB126 that has a two-nucleotide deletion in the open reading frame, which generates an abnormal mRNA. The allele frequency of this variant sequence was high in both a European (0.47) and a Chinese (0.45) population cohort. Binding of the Agaricus bisporus lectin to the sperm surface glycocalyx was significantly lower in men with the homozygous variant (del/del) genotype than in those with either a del/wt or a wt/wt genotype, suggesting an altered sperm glycocalyx with fewer O-linked oligosaccharides in del/del men. Moreover, sperm from del/del carriers exhibited an 84% reduction in the rate of penetration of a hyaluronic acid gel, a surrogate for cervical mucus, compared to the other genotypes. This reduction in sperm performance in hyaluronic acid gels was not a result of decreased progressive motility (average curvilinear velocity) or morphological deficits. Nevertheless, DEFB126 genotype and lectin binding were correlated with sperm performance in the penetration assays. In a prospective cohort study of newly married couples who were trying to conceive by natural means, couples were less likely to become pregnant and took longer to achieve a live birth if the male partner was homozygous for the variant sequence. This common sequence variation in DEFB126, and its apparent effect of impaired reproductive function, will allow a better understanding, clinical evaluation, and possibly treatment of human infertility.

The aim of this study was to determine the association between coding variants in the human tissue kallikrein 1 (KLK1) gene and baseline blood pressure (BP) and antihypertensive response to irbesartan treatment in Chinese hypertensive patients. A total of 1061 hypertensives were recruited and received daily oral dosage of 150 mg irbesartan for 4 weeks. Predose BPs, BPs and blood irbesartan concentrations at postdose on the 28th day were all measured. Common functional single-nucleotide polymorphisms (SNPs) in the KLK1 gene were genotyped. On the basis of the HapMap data of Han Chinese in the Beijing population, two non-synonymous polymorphisms with minor allele frequency>0.1, SNP rs5517 (Glu162Lys) and rs5516 (Gln121Glu), were selected. Those with GG genotype in the rs5516 locus had higher average baseline systolic BP (SBP) than CC subjects (β±s.e.: 5.0±2.3, P=0.033); and no associations of rs5517 with baseline BP (diastolic BP (DBP) and SBP) and BP responses, or rs5516 with baseline DBP and BP response were observed. In a haplotype-based association test for the KLK1 gene, the Haplo-special score analyses identified that haplotype AG was marginally associated with SBP response (specific score: 1.75 for P=0.08), but not with DBP response. We did not find any associations between haplotypes (GC and AC) and BP responses. The Haplo-GLM analyses showed that, compared with haplotype GC subjects, the subjects with haplotype AG had a marginally greater SBP response (adjusted β±s.e.: 1.81±0.97, P=0.06), but DBP response did not differ. This study suggests that rs5516 in the KLK1 gene may be involved in the development of essential hypertension and in the regulation of SBP-lowering response to irbesartan in Chinese hypertensives.

The development of essential hypertension (EH) and inter-individual differences in response to antihypertensive treatment may partly result from genetic heterogeneity. In this study, we conducted an investigation of the combined effects of 5, 10-methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase (MS) A2756G polymorphisms on baseline blood pressure (BP) and BP response to antihypertensive Benazepril treatment in 823 Chinese hypertensive patients with a fixed daily dosage of 10 mg for 15 consecutive days. When MTHFR C677T and MS A2756G polymorphisms were modelled together with adjustment for important covariates, only MTHFR C677T was associated with baseline systolic BP (SBP) (β (s.e.)=2.84 (1.10), P=0.0096) or baseline diastolic BP (DBP) (β (s.e.)=2.19 (0.65), P=0.0008). Modelled together with adjustment for important covariates, MTHFR C677T and MS A2756G polymorphisms were both independently associated with increased DBP response (baseline minus post-treatment) to Benazepril treatment (C677T: β (s.e.)=1.58 (0.76), P=0.038; A2756G: β (s.e.)=2.14 (0.89), P=0.016). Neither polymorphism was associated with SBP response to Benazepril treatment. There were no significant interactions or effect modification between MTHFR C677T and MS A2756G gene polymorphisms in models of baseline SBP, baseline DBP or DBP response to Benazepril treatment. Our results suggest that the effects of MTHFR C677T and MS A2756G gene polymorphisms may have pivotal roles in the aetiology of EH and BP response to Benazepril treatment.

Many Americans are exposed to low levels of organophosphorous (OP) pesticides. It is unclear whether these exposures impact sperm production. We investigated whether there was an association between urinary OP insecticide metabolites and sperm concentration and motility in newly married men from a rural area of eastern People's Republic of China. Ninety-four cases and 95 controls were included based on their median residual value of sperm concentration and motility after adjusting for relevant covariates. Their urine was analyzed for six dialkylphosphate (DAP) compounds. After adjustment for demographic and exposure variables, the odds of being a case were greater (odds ratio=1.30, 95% confidence interval 1.02-1.65) in men with higher urinary concentrations of dimethylphosphate (DMP) compared to men with lower levels. No significant differences between cases and controls were found among the other DAP concentrations. DMP exposure and sperm concentration and motility should be explored further in environmental exposure studies., (Copyright © 2010 Elsevier Inc. All rights reserved.)

This study investigated whether high central adiposity was associated with prediabetes and decreased insulin sensitivity (IS) in both normal-weight (body mass index [BMI] <23 kg/m(2)) and overweight (BMI >or=23 kg/m(2)) rural Chinese women. Adipose variables measured by dual-energy x-ray absorptiometry (percentage body fat, percentage lower-body fat [%LF], and percentage trunk fat [%TF]) and general adipose variables (BMI and waist circumference) were used for examining the association of adiposity with prediabetes among 4071 rural Chinese women aged 20 to 60 years. Furthermore, the association of adiposity with IS was tested in both normal- and overweight women with normal glucose tolerance. BMI was highly correlated with percentage body fat and waist circumference, but was weakly correlated with %LF and %TF. Both high %TF (top quartile of %TF) and low %LF (lower 3 quartiles of %LF) were associated with higher prevalence of prediabetes in both normal- and overweight women. Compared with normal-weight women in low %TF, the odds of prediabetes were similarly increased for women with high %TF regardless of whether they were overweight (odds ratio [95% confidence interval] = 1.6 [1.3-2.0]) or not (odds ratio [95% confidence interval] = 1.5 [1.2-2.0]). Similarly, among 3280 women with normal glucose tolerance, high %TF was associated with increased fasting insulin, 2-hour oral glucose tolerance test insulin, and homeostasis model assessment of insulin resistance regardless of weight status (normal or overweight). Among relatively lean, rural Chinese women, high %TF was associated with increased odds of prediabetes and lower IS regardless of weight status (normal or overweight).

Background: Most studies linking obesity and metabolic syndrome (MS) have used body mass index (BMI) and waist circumference (WC) to measure obesity. While BMI is correlated with direct measures of total and central adiposity, it is influenced by lean body and bone mass. We hypothesize that direct measures of adiposity may help develop further insight into the link between obesity and MS, thus more accurately identifying individuals at high risk for MS., Aim of the Study: We examined how surrogate and direct measures of adiposity were associated with MS risk and if direct adiposity measures enhanced BMI and WC identification of MS risk., Methods: 3,734 Chinese female twins aged 20-39 years were studied. Percent body fat (%BF) and proportion of trunk fat to total BF (%TF) were assessed by DEXA. Graphic plots and generalized estimating equations were used to examine the associations of adiposity measures with MS and its components. Concordance of adiposity measures and MS abnormalities between monozygotic (MZ) and dizygotic (DZ) twin pairs were compared., Results: The prevalence of MS increased for high BMI (>or=23 kg/m(2)), %BF (>or=32), WC (>or=80 cm), and (to a lesser degree) %TF (>or=50). Below those thresholds, the prevalence of MS was low (0-5.3%). %TF was independently associated with higher risk of MS and its components even after adjusting for BMI and WC. As a result, among women with normal BMI and WC, high %TF was associated with 1.3-2.0-fold elevated risk of MS components. In contrast, women with high BMI but normal WC and %TF neither have significantly increased risk of MS, nor for any component other than high BP. MZ twins showed higher concordance for MS and its components than DZ twins., Conclusions: In this lean Chinese rural female sample, BMI >or= 23 and WC >or= 80 were associated with a markedly increased risk of MS, which was further enhanced by elevated %TF. Even in women with a normal BMI and WC, %TF was independently associated with MS and its components. Twin analysis findings suggest that adiposity measurements and MS risk are influenced by genetics.

Background: Vitamin nutritional status may influence some xenobiotic metabolism or vice versa., Methods: This analysis examines the relationship between B-vitamin concentrations and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDT) isomers and metabolites in healthy women. Serum pp'DDT, pp'DDE, pp'DDD, op'DDT, op'DDE, and serum folate, cysteine, and vitamins B6 and B12 were measured in 296 nonsmoking female textile workers (21-34 yr) in Anhui, China. Mean (SD) age and body mass index of this cohort were 24.9 (1.5) y and 19.7 (2.0) kg/m(2), respectively., Results: Median pp'DDT, pp'DDE, pp'DDD, op'DDT, and op'DDE were 1.5, 29.2, 0.22, 0.17, and 0.09 ng/g, respectively. Median folate and cysteine were 9.2 and 200.0 nmol/L, respectively. Folate was significantly inversely associated with pp'DDT and pp'DDE: beta (95% confidence interval [CI]) = -0.23 (-0.39, -0.07) and -0.20 (-0.36, -0.05), respectively, and it was marginally associated with pp'DDD. Cysteine was significantly inversely associated with pp'DDT, beta (95% CI) = -0.69 (-1.00, -0.37); pp'DDE, beta (95% CI) = -0.32 (-0.62, -0.02); pp'DDD, beta (95% CI) = -0.31 (-0.59, -0.03); and op'DDT, beta (95% CI) = -0.35 (-0.68, -0.02)., Conclusions: Folate and cysteine are independently inversely associated with DDT isomers, adjusting for vitamins B6 and B12, age, and body mass index. These nutrients may play a role in DDT metabolism; however, it is also possible that DDT may exert a negative impact on folate and cysteine levels. Longitudinal studies are needed to ascertain the direction of this association.

Introduction: The menstrual cycle involves periodic fluctuations in estrogen and progesterone levels. Longer cycles have been associated with longer follicular phase, delayed estrogen peak and a lower mean oestradiol level of the entire cycle., Methods: We hypothesized that prolonged menstrual cycle length is associated with decreased bone mineral density (BMD) in a population of pre- and perimenopausal women. This population-based cross-sectional study was conducted in rural Anhui province, China. It includes 4,771 women, aged 30 to 49 years, who did not smoke or drink alcohol, and did not use oral contraceptives or breastfeed during the previous year. Dual-energy X-ray absorptionometry (DEXA) BMD measurements were taken at four skeletal sites: whole body, total hip, femoral neck and lumbar spine. Menstrual cycle characteristics (polymenorrhea, short normal, long normal, oligomenorrhea, 90-day amenorrhea, irregular cycle) in the prior year were assessed by questionnaire., Results: Prolonged menstrual cycle was consistently associated with decreased BMD at whole body, total hip, and femoral neck in both age 30-39, and age 40-49 stratum (p(trend)<0.05). Prolonged menstrual cycle was also associated with decreased lumbar spine BMD for women aged 40-49 (p(trend)<0.05). Among women with normal cycles aged 30-39, menstrual cycle length in the previous year was inversely associated with whole-body BMD (p<0.05). Women with 90-day amenorrhea had significantly lower mean total hip and femoral neck BMD relative to women with short normal cycles in the 30-39 age group; and had significantly lower whole body and total hip BMD relative to short normal cycles in the 40-49 age group. BMD in polymenorrheic women did not differ from BMD in women with short normal cycles at any of the skeletal sites., Conclusions: We conclude that prolonged menstrual cycle length is associated with decreased BMD in pre- and perimenopausal women in this population.

Osteoporosis is a major public health concern and its prevalence can be predicted based on forearm bone mineral density (BMD). This study is to investigate the familial aggregation of forearm BMD in a population-based, cross-sectional study in Anhui, China. Information on sociodemographic and environmental variables was obtained from 1,636 subjects from 409 nuclear families (including mother, father, and their first two children) by a standardized questionnaire. The forearm BMD was measured by peripheral dual-energy X-ray absorptiometry (pDXA). Using generalized additive models with a sequential adjustment for covariates, it was clearly indicated that the forearm BMD of the mother, the father, and the first sibling each had a significant and independent relation to the forearm BMD of the second sibling. Furthermore, using multiple logistic regression, the second sibling had an odds ratio (OR) of 5.3 (95%CI: 2.0-14.5) of having an extremely low (bottom 10th percentile) proximal forearm BMD and an OR of 4.3 (95%CI: 1.6-12.0) of having an extremely low distal forearm BMD when the parental mean forearm BMD was low and the first sibling's forearm BMD was low. Our findings showing strong familial aggregation of both proximal and distal forearm BMD values suggest that genetic factors play a significant role in determining both traits.

Background: There is growing concern that poisoning and other adverse health effects are increasing because organophosphorous (OP) insecticides are now being used in combination with pyrethroid (PYR) insecticides to enhance the toxic effects of PYR insecticides on target insects, especially those that have developed PYR resistance., Objectives: We conducted a pilot biomonitoring study to determine whether men in our reproductive cohort study were being exposed to pesticides environmentally by virtue of frequenting an agricultural setting., Methods: We screened 18 randomly selected urine samples collected from male participants of reproductive age for 24 parent compounds and metabolites of pesticides and examined the results in relation to sperm concentration., Results: Results showed high prevalence of exposure to OP and PYR pesticides and our preliminary analyses provided some suggestion that the higher exposure group had lower sperm concentration., Conclusions: The potential of OP/PYR mixtures to have enhanced human toxicity needs more research attention.

Background: Knowledge is limited of how estrogen and progesterone variability in fertile women are associated with achieving pregnancy., Methods: From 1996 to 1998, we enrolled 347 textile workers without hormone treatment in Anhui, China, who provided daily urine and data upon stopping contraception for up to 1 year until clinical pregnancy. Urinary hCG was assayed to detect conception and early pregnancy losses. We compared urinary concentrations of estrone conjugates (E(1)C) and pregnanediol-3-glucuronide (PdG) in 266 clinical pregnancies, 63 early pregnancy losses and 272 non-conception cycles from 347 women and also in 94 clinical pregnancy and 94 non-conception cycles from the same women., Results: Using generalized estimating equations and relative to 266 clinical pregnancy cycles, log(E(1)C) was lower in 272 non-conception cycles [beta = -0.3 ng/mg creatinine (Cr); SE = 0.1; P < 0.0001]. On average, daily E(1)C was 18 ng/mg Cr lower in non-conception cycles than in clinical pregnancy cycles. Relative to 94 clinical pregnancy cycles, log(E(1)C) was lower in 94 non-conception cycles (beta = -0.4 ng/mg Cr; SE = 0.1; P < 0.0001) from the same women (average difference in daily E(1)C was 20 ng/mg Cr). The odds of E(1)C less than the 10th percentile (<30 ng/mg Cr) were higher in early pregnancy loss cycles [odds ratio (OR) = 4.8; P = 0.0027] than in clinical pregnancy cycles in the early luteal phase. Compared with clinical pregnancy cycles, log(PdG) concentrations were lower in non-conception cycles during the follicular phase, but this analysis lacked power for multiple testing., Conclusions: Estrogen concentrations varied from cycle to cycle, and higher estrogen was associated with achieving clinical pregnancy.

Background: Higher fat mass may be an independent risk factor for osteoporosis and osteoporotic fractures., Objective: We aimed to determine the independent contribution of fat mass to osteoporosis and to estimate the risk of osteoporotic fractures in relation to body weight, lean mass, and other confounders., Design: This was a community-based, cross-sectional study of 7137 men, 4585 premenopausal women, and 2248 postmenopausal women aged 25-64 y. Total-body and hip bone mineral content (BMC) and bone mineral density (BMD) and body composition were measured by dual-energy X-ray absorptiometry. Serum lipids were measured. Sex- and menopause-specific multiple generalized linear models were applied., Results: Across 5-kg strata of body weight, fat mass was significantly inversely associated with BMC in the whole body and total hip. When we compared the highest quartile with the lowest quartile of percentage fat mass in men, premenopausal women, and postmenopausal women, the adjusted odds ratios (95% CIs) of osteoporosis defined by hip BMD were 5.2 (2.1, 13.2), 5.0 (1.7, 15.1), and 6.9 (4.3, 11.2), respectively. Significant linear trends existed for higher risks of osteoporosis, osteopenia, and nonspine fractures with higher percentage fat mass. Significant negative relations were found between whole-body BMC and cholesterol, triacylglycerol, LDL, and the ratio of HDL to LDL in all groups., Conclusions: Risks of osteoporosis, osteopenia, and nonspine fractures were significantly higher for subjects with higher percentage body fat independent of body weight, physical activity, and age. Thus, fat mass has a negative effect on bone mass in contrast with the positive effect of weight-bearing itself.

Background: Although dichlorodiphenyl trichloroethane (DDT) exposure is known to affect human endocrine function, few previous studies have investigated the effects of DDT exposure on age at menarche or menstrual cycle length., Methods: A cross sectional study was conducted to study the effects of DDT exposure on age at menarche and menstrual cycle length among 466 newly married, nulliparous female Chinese textile workers aged 20-34 years enrolled between 1996 and 1998. Serum was analysed for DDT and its major metabolites. Multivariate linear regression was used to estimate DDT exposure effects on age at menarche and multivariate logistic regression was used to estimate DDT exposure effects on odds of experiencing short or long cycles., Results: Relative to those in the lowest DDT quartile, the adjusted mean age at menarche was younger in those in the fourth quartile (-1.11 years). Modeled as a continuous variable, a 10 ng/g increase in serum DDT concentration was associated with an adjusted reduction in age at menarche of 0.20 years. Relative to those in the lowest DDT quartile, odds of any short cycle (<21 days) in the previous year were higher for those in the fourth quartile (odds ratio = 2.78; 95% CI 1.07 to 7.14). There were no associations between serum DDT concentrations and odds of experiencing a long cycle (>40 days)., Conclusion: Results suggest that DDT exposure was associated with earlier age at menarche and increased risk of experiencing a shortened menstrual cycle.

Previous studies of pregnancy losses and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) were limited because they did not include losses prior to clinical detection of pregnancy and because exposures were measured after the pregnancies of interest. The authors examined the association of preconception serum total DDT (sum of DDT isomers and metabolites) concentration and subsequent pregnancy losses in 388 newly married, nonsmoking, female textile workers in China between 1996 and 1998. Upon stopping contraception, subjects provided daily urine specimens and records of vaginal bleeding for up to 1 year or until clinical pregnancy. Daily urinary human chorionic gonadotropin was assayed to detect conception and early pregnancy losses, and pregnancies were followed to detect clinical spontaneous abortions. There were 128 (26%) early pregnancy losses in 500 conceptions and 36 (10%) spontaneous abortions in 372 clinical pregnancies. Subjects were grouped in tertiles by preconception serum total DDT concentration (group 1: 5.5-22.9 ng/g; group 2: 23.0-36.5 ng/g; group 3: 36.6-113.3 ng/g). Compared with group 1, group 2 had adjusted relative odds of early pregnancy losses of 1.23 (95% confidence interval (CI): 0.72, 2.10), and group 3 had adjusted odds of 2.12 (95% CI: 1.26, 3.57). The relative odds of early pregnancy losses associated with a 10-ng/g increase in serum total DDT were 1.17 (95% CI: 1.05, 1.29). The small number of spontaneous abortions following clinical detection of pregnancy were not associated with serum total DDT. In this population, there was a positive, monotonic, exposure-response association between preconception serum total DDT and the risk of subsequent early pregnancy losses.

Background: Basic health indicators, such as body mass index (BMI), have been associated with serum 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane/1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDT/DDE) levels; however, both positive and inverse associations of BMI with serum DDT/DDE have been reported. Given the association of BMI with a number of outcomes, it may confound studies of DDT/DDE-associated health effects. We investigated the relationship of BMI with serum DDT/DDE accounting for other determinants of exposure among women with relatively recent environmental exposures to DDT., Methods: Serum DDT/DDE was analyzed in 466 nonsmoking, nulliparous women recruited from Anhui province in China between 1996 and 1998 as part of a reproductive health study of textile workers. The women in the sample were born between 1963 and 1977, 8 to 21 years before China's 1984 DDT ban. We used multivariate linear regression to investigate associations of BMI, age, and birth year with serum DDT/DDE., Results: Mean (SD) serum total DDT concentration was 32 ng/g (17.8 ng/g). Birth year showed an inverse relationship with serum DDT independent of age. Despite limited variability in BMI, there was a consistent inverse relationship between BMI and serum DDT. Specifically, each kg/m(2) increase in BMI was associated with a -1.34 ng/g (95% confidence interval, -2.12 to -0.56 ng/g) decrease in serum total DDT., Conclusions: There were high total DDT levels in this sample of nulliparous Chinese women relative to Western populations, birth year was more strongly associated with serum DDT than age, and BMI was inversely related to serum DDT in this study.