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Epigenetic changes may account for the doubled risk to develop schizophrenia in individuals exposed to famine in utero. We therefore investigated DNA methylation in a unique sample of patients and healthy individuals conceived during the great famine in China. Subsequently, we examined two case-control samples without famine exposure in whole blood and brain tissue. To shed light on the causality of the relation between famine exposure and DNA methylation, we exposed human fibroblasts to nutritional deprivation. In the famine-exposed schizophrenia patients, we found significant hypermethylation of the dual specificity phosphatase 22 (DUSP22) gene promoter (Chr6:291687-293285) (N = 153, p = 0.01). In this sample, DUSP22 methylation was also significantly higher in patients independent of famine exposure (p = 0.025), suggesting that hypermethylation of DUSP22 is also more generally involved in schizophrenia risk. Similarly, DUSP22 methylation was also higher in two separate case-control samples not exposed to famine using DNA from whole blood (N = 64, p = 0.03) and postmortem brains (N = 214, p = 0.007). DUSP22 methylation showed strong genetic regulation across chromosomes by a region on chromosome 16 which was consistent with new 3D genome interaction data. The presence of a direct link between famine and DUSP22 transcription was supported by data from cultured human fibroblasts that showed increased methylation (p = 0.048) and expression (p = 0.019) in response to nutritional deprivation (N = 10). These results highlight an epigenetic locus that is genetically regulated across chromosomes and that is involved in the response to early-life exposure to famine and that is relevant for a major psychiatric disorder.

Introduction This cross-sectional survey among Chinese university students aimed to estimate the prevalence and risk factors of major depressive disorder (MDD) among undergraduates, in order to provide basic information for the prevention and treatment of depression among the college-aged population. Methods A total of 2,046 undergraduates were interviewed face to face using the World Health Organization Composite International Diagnostic Interview Version 3.0 (WHO-CIDI, version 3.0). Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria were used to diagnose MDD. Logistic regression was used to evaluate the associations between MDD and selected correlates. Results The survey response rate was 90.1% (N = 1,843). The prevalence rates of MDD were 3.9% (lifetime), 2.4% (12 months) and 0.4% (30 days). No significant gender or age differences were found in prevalence rates. No sociodemographic characteristics were related to the lifetime prevalence of MDD. In contrast, family structure and environment factors specifically being from a single-parent family (odds ratio [OR] = 2.513, confidence interval [CI] = 1.404–2.500), parents having mental problems (OR = 1.809, CI = 1.104–2.964), and physical punishment (OR = 1.789, CI = 1.077–3.001) were associated with higher lifetime prevalence of MDD. Discussion These findings showed a relatively lower prevalence of DSM-IV/CIDI MDD in this sample of Chinese undergraduates than that reported for students in other countries. However, the prevalence rate for university students was higher than that reported for general Chinese population. Family structure and socio-environmental factors in the student's family of origin significantly correlated with the lifetime prevalence of MDD.

Background Ghrelin, in humans, is a hormone secreted from the stomach with an orexigenic effect, which is good for digestion and absorption, as well as regulating physical growth, metabolism, and energy balance. It is also involved in the development of metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM). This study assessed the association between single nucleotide variants of the GHRL gene and the risk of metabolic syndrome in a Han Chinese population. Methods A case-control study was performed on 3780 Han Chinese comprising 1813 MetS cases and 1967 controls. Three missense polymorphisms in GHRL (rs26802, rs10490816, and rs696217) were selected, and the association between these polymorphisms and the risk of MetS was investigated. Metabolic syndrome was defined according to the criteria of the International Diabetes Federation (IDF). Results Using Pearson's 2 test, we found that there were no significant differences in genotype distributions and allele frequencies between cases and controls (all p > 0.05). There were also no significant differences in haplotype distributions between MetS cases and healthy controls. Furthermore, we confirmed that rs26802 of the GHRL gene is associated with body mass index (BMI), waist circumference, systolic blood pressure (SBP), and fasting glucose; rs10490816 is associated with triglycerides (TG) and total cholesterol (TC); while rs696217 is associated with hip circumference and fasting glucose. Conclusions We concluded that mutations in the GHRL gene did not confer risk for MetS in our study population. Therefore, functional analysis and replication studies in other populations are needed to further investigate the exact role of the GHRL gene in MetS.

Rural–urban differences in the prevalence of chronic diseases in the adult population of northeast China are examined. The Jilin Provincial Chronic Disease Survey used personal interviews and physical measures to research the presence of a range of chronic diseases among a large sample of rural and urban provincial residents aged 18 to 79 years (N = 21 435). Logistic regression analyses were used. After adjusting for age and gender, rural residents had higher prevalence of hypertension, chronic ischemic heart disease, cerebrovascular disease, chronic low back pain, arthritis, chronic gastroenteritis/peptic ulcer, chronic cholecystitis/gallstones, and chronic lower respiratory disease. Low education, low income, and smoking increased the risk of chronic diseases in rural areas. Reducing rural–urban differences in chronic disease presents a formidable public health challenge for China. The solution requires focusing attention on issues endemic to rural areas such as poverty, lack of chronic disease knowledge, and the inequality in access to primary care.

Diagnosis of schizophrenia does not have a clear objective test at present, so we aimed to identify the potential biomarkers for the diagnosis of schizophrenia by comparison of serum protein profiling between first-episode schizophrenia patients and healthy controls. The combination of a magnetic bead separation system with matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF-MS) was used to analyze the serum protein spectra of 286 first-episode patients with schizophrenia, 41 chronic disease patients and 304 healthy controls. FlexAnlysis 3.0 and ClinProTools(TM) 2.1 software was used to establish a diagnostic model for schizophrenia. The results demonstrated that 10 fragmented peptides demonstrated an optimal discriminatory performance. Among these fragmented peptides, the peptide with m/z 1206.58 was identified as a fragment of fibrinopeptide A. Receiver operating characteristic analysis for m/z 1206.58 showed that the area under the curve was 0.981 for schizophrenia vs healthy controls, and 0.999 for schizophrenia vs other chronic disease controls. From our result, we consider that the analysis of serum protein spectrum using the magnetic bead separation system and MALDI-TOF/TOF-MS is an objective diagnostic tool. We conclude that fibrinopeptide A has the potential to be a biomarker for diagnosis of schizophrenia. This protein may also help to elucidate schizophrenia disease pathogenesis.

Papillary thyroid cancer (PTC) is the most common type of thyroid cancer, yet few genetic markers of PTC risk useful for screening exist. Our study aimed to evaluate the association between single nucleotide polymorphisms (SNPs) of the ataxia telangiectasia mutated (ATM) gene and PTC risk. 358 patients with PTC and 360 healthy controls were included in the case-control study. Four ATM SNPs (rs664677, rs373759, rs4988099, and rs189037) were genotyped by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). The analysis of genetic data was performed using the SNPStats program. The allele frequencies and genotype distributions of the four ATM SNPs were not different between PTC patients and controls. We did not observe any tendency of increasing the frequency of the risk allele from controls, patients without metastasis to patients with metastasis (P(trend) > 0.05). Interestingly, the AG genotype of rs373759 was associated with PTC risk under an overdominant model of inheritance (adjusted OR = 1.38; 95 % CI, 1.03-1.87; P = 0.03). No haplotype was observed to be significantly associated with PTC risk. Our results suggest that heterozygosity for the ATM rs373759 polymorphism may be a potential risk factor for PTC.

Our previous studies using the mass spectrum analysis provided evidence that fibrinopeptide A (FPA) could be a potential biomarker for schizophrenia diagnosis. We sought further to demonstrate that variants in the fibrinogen alpha chain gene (FGA) coded FPA might confer vulnerability to schizophrenia. 1,145 patients with schizophrenia and 1,016 healthy volunteers from the Han population in Northeast China were recruited. The association of three tag single nucleotide polymorphisms (SNPs) (rs2070011 in the 5′UTR, rs2070016 in intron 4, and rs2070022 in the 3′UTR) in FGA and schizophrenia was examined using a case-control study design. Genotypic distributions of these three SNPs were not found to be significantly different between cases and controls (rs2070011: χ2=1.28, P=0.528; rs2070016: χ2=4.11, P=0.128; rs2070022: χ2=1.23, P=0.541). There were also no significant differences in SNP allelic frequencies between cases and controls (all P>0.05). Additionally, the frequency of haplotypes consisting of alleles of these three SNPs was not significantly different between cases and healthy control subjects (global χ2=9.27, P=0.159). Our study did not show a significant association of FGA SNPs with schizophrenia. Future studies may need to test more FGA SNPs in a larger sample to identify those SNPs with a minor or moderate effect on schizophrenia.

// Rui Liu 1, * , Lifeng Ning 1, 2, * , Xiaoli Liu 3 , Huiping Zhang 4 , Yaqin Yu 1 , Shangchao Zhang 1 , Wenwang Rao 1 , Jieping Shi 1 , Hui Sun 3 , Qiong Yu 1 1 Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun 130021, China 2 National Research Institute for Family Planning, Beijing 100081, China 3 Jilin Provincial Key Laboratory of Surgical Translational Medicine, China-Japan Union Hospital, Jilin University, Changchun 130033, China 4 Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA * These authors have contributed equally to this work Correspondence to: Qiong Yu, email: yuqiong@jlu.edu.cn Keywords: papillary thyroid carcinoma, nodular goiter, VEGFA, SNPs, Han Chinese Received: September 01, 2016 Accepted: January 06, 2017 Published: February 02, 2017 ABSTRACT The aim of the present study was to investigate whether genetic variants in the vascular endothelial growth factor A gene ( VEGFA ) were risk factors for papillary thyroid carcinoma (PTC) or nodular goiter (NG) in Han Chinese. A total of 2,319 subjects (861 PTC patients, 562 NG patients, and 896 healthy controls) were included. Five tag single nucleotide polymorphisms (tagSNPs: rs3024997, rs3025040, rs833070, rs25648, and rs10434) in VEGFA were genotyped. SNP rs3025040 T allele was associated with a decreased risk of NG ( P

Introduction To explore the association between histone deacetylase-2 (HDAC2) and histone deacetylase-3 (HDAC3) gene polymorphisms and schizophrenia. Methods A total of 208 family trios consisting of fathers, mothers and affected offspring with schizophrenia were recruited as our subjects. Four tag SNPs on HDAC2 (rs10499080, rs6568819, rs2499618 and rs13204445) and two tag SNPs on HDAC3 (rs11741808, rs2530223) genes were selected. The Mass ARRAY Assay Design software (Sequenom) was used to design amplification and allele specific extension primers. The Hardy-Weinberg equilibrium (HWE) for genotypic distributions was tested using the chi-square goodness-of-fit test. Allelic association for a single tag SNP was analyzed by using family-based association tests including the haplotype-based haplotype relative risk (HHRR) test and the transmission disequilibrium test (TDT). Results The genotypic distributions of HDAC2 SNPs rs6568819, rs2499618 and rs13204445 and HDAC3 SNPs rs11741808 and rs2530223 were all in Hardy-Weinberg equilibrium (P > 0.05). HHRR analysis revealed no associations between the SNPs and schizophrenia (P > 0.05). In addition, the TDT did not show any significant associations between HDAC2 and HDAC3 SNPs and schizophrenia (P > 0.05). Discussion HDAC2 and HDAC3 might not be associated with schizophrenia in the Chinese population.

Abnormal phospholipid metabolism in the brain plays an important role in neuropsychiatric diseases. Phospholipase A2 (PLA2) is a crucial element for normal neuro-physiological function. This study aims to investigate the genetic association between the polymorphism of cytosolic phospholipase A2 (cPLA2) family genes and schizophrenia among Han Chinese in the northern part of China. The polymerase chain reaction-based ligase detection reaction (PCR-LDR) was applied to detect the genotype ten single nucleotide polymorphisms (SNPs) of cPLA2 family genes among 201 pedigrees consisting of fathers, mothers and affected offsprings with schizophrenia. The pedigrees were collected from 2000 to 2006. Haplotype relative risk (HRR) test, transmission disequilibrium test (TDT), haplotype transmission analysis and multiple locus analysis were conducted to analyze the genotyping data. The genotypic frequency of cPLA2 gene did not deviate from Hardy-Weinberg equilibrium either in case or control group. HRR and TDT showed that the ten SNPs were not associated with schizophrenia (P > 0.05). Analysis for haplotype transmission showed that no haplotype system was associated with schizophrenia (P > 0.05). The conditioning on allele (COA) and conditioning on gene (COG) tests showed disease associations with the haplotype of rs2162886-rs1668589, rs891014-rs1668589 and rs2307279-rs7542180 (χ2 = 6.913, P = 0.032; χ2 = 8.393, P = 0.015; χ2= 8.447, P = 0.038). Our data suggest that many loci in the cPLA2 family genes may be associated with schizophrenia.

Background: The present study aimed to investigate the prevalence and associated socio-demographic factors of passive smoking among women in Jilin Province, China. Methods: A cross-sectional study was conducted in 2012, using a self-reported questionnaire interview. A representative sample of 9788 non-smoking women aged 18–79 years was collected in Jilin Province of China by a multistage stratified random cluster sampling design. Descriptive data analysis and 95% confidence intervals (CI) of prevalence/frequency were conducted. Multivariable logistic regressions were used to examine the associated socio-demographic factors of passive smoking. Results: The overall prevalence of passive smoking among non-smoking women in Jilin Province was 60.6% (95% CI: 59.3–61.8), 58.3% (95% CI: 56.7–59.9) from urban areas, and 63.4% (95% CI: 61.6–65.3) from rural areas. Twenty-six percent (95% CI: 24.9–27.1) of the non-smoking women reported daily passive smoking, of which 42.9% (95% CI: 41.6–44.1) reported passive smoking at home, and 5.1% (95% CI: 4.5–5.7) reported passive smoking in restaurants. Women in urban areas were less likely to be passive smokers than those in rural ones (OR-Odds Ratio: 0.825, 95% CI: 0.729–0.935), elderly women were less likely to be passive smokers than younger women (55–64 years OR: 0.481, 95% CI: 0.342–0.674, 65–79 years OR: 0.351, 95% CI: 0.241–0.511). Seperated/divorced women were less likely to be passive smokers (OR: 0.701, 95% CI: 0.500–0.982), and widowed women (OR: 0.564, 95%CI: 0.440–0.722), as the married were the reference group. Retired women second-hand smoked due to environmental causes significantly less than manual workers (OR: 0.810, 95% CI: 0.708–0.928). Women with a monthly family income of more than 5000 RMB were less likely to be passive smokers than those with an income less than 500 RMB (OR: 0.615, 95% CI: 0.432–0.876). Conclusions: The prevalence of passive smoking is lower than that reported in 2010 Global Adult Tobacco Survey (GATS) China, but passive smoking is still prevalent and has been an acute public health problem among non-smoking women in Jilin Province, China. Our findings suggest an urgent need for tobacco control and the efforts of public health should be both comprehensive and focus on high-risk populations in Jilin Province, China.

This work reviewed all the reports on the NOTCH4 gene in schizophrenia, which have been published since the gene was found to be associated with illness among a British population in 2000. The results from independent studies were inconsistent. Allelic heterogeneity, clinical diagnosis, ethnical backgrounds, and linkage disequilibrium (LD) structures in the human genome may be major reasons for poor replication. A couple of studies suggested that the NOTCH4 gene could play a role in a subgroup of the disease, such as early-onset schizophrenia and negative symptoms. A single study revealed a weak association of the NOTCH4 gene with frontal lobe brain volumes and a strong association with frontal lobe cognitive performance. A meta-analysis showed stronger evidence of the NOTCH4 association in family-based studies than in case-control studies. In a previous study, we found that rs520692, a single nucleotide polymorphism (SNP) at the NOTCH4 locus, was associated with schizophrenia in a Chinese population. In the present study, we applied a large sample size to re-evaluate our initial findings and then confirmed the rs520692 association with illness. The pairwise measures did not show strong LD between paired SNPs although the SNPs tested are located within a 34-kb region, suggesting that LD within the NOTCH4 gene has been broken rapidly by historical recombination in the Chinese population. Taken together, the NOTCH4 gene may be associated with schizophrenia but how the gene contributes to the etiology of the illness needs a further investigation.

The present study detected 9 single nucleotide polymorphisms (SNPs) at the PLA2G4C and PLA2G6 loci among 240 Chinese parent-offspring trios of Han descent. Of these 9 SNPs, 5 showed highly polymorphic in the Chinese population. They were then applied as genetic markers to test the genetic association of these two calcium-independent cytosolic PLA2 genes with schizophrenia. The transmission disequilibrium test (TDT) showed that rs1549637 at the PLA2G4C locus was the only SNP associated with the illness (chi(2) = 5.63, P = 0.018). The global P-value was 0.082 for 1000 permutations with the TDT analysis. Neither the conditional on allele test nor the conditional on genotype test showed a disease association for the combination of these two genes. Because the PLA2G4C association is so weak, this initial finding should be interpreted with caution.

The present study was undertaken to replicate an association between the PTGS2/PLA2G4A locus and schizophrenia among a Chinese population. We recruited 168 Chinese parent-offspring trios of Han descent, consisting of fathers, mothers and affected offspring with schizophrenia. Of 3 informative SNPs genotyped, no one showed allelic association with schizophrenia; the haplotype analysis also failed to capture a haplotypic association with the illness. Because the frequencies of alleles and genotypes of SNPs analyzed differ in the Chinese population as compared with a British population that initially showed the genetic association between the PTGS2/PLA2G4A locus and schizophrenia, the ethnic background may be a major reason for poor replication of the initial finding.

The transmission properties of rectangular one-dimensional unperforated metallic periodic structures for frequencies close to the surface plasmon band are investigated experimentally and theoretically. The results reveal that it is possible to obtain unexpectedly large transmissions through thick unperforated metallic structures. The mechanisms of enhanced transmissions are attributed to resonant excitations of three kinds of plasmon radiations: coupled surface plasmon polaritons, horizontal localized groove plasmon mode, and vertical localized groove plasmons mode. Once the surface plasmon polaritons and the vertical groove plasmon modes are excited simultaneously, the transmission approaches to maximum at the coincident condition.

The near-field distribution of surface plasmon polariton (SPP) on metallic photonic crystal slabs has been studied. Preliminary numerical simulations indicate that the interference of SPP on the exit side of metallic photonic crystal slabs can redistribute the illumination light into nano-scale spatial distribution, which beats the Rayleigh diffraction limit. The electric field distribution of SPP with a resolution of 50 nm was measured by recording the high intensity range into photoresist with a wavelength of 436 nm. Because of the small wavelength of the plasmon wave, a much higher spatial resolution can be obtained, which can provide a new nano-fabrication or nano-storage method by using optical light with a long wavelength.

This study investigates the genetic association between catechol-O-methyltransferase (COMT) gene polymorphisms and neurotic disorders. Data were derived from a case-control association study of 255 undergraduates affected by neurotic disorders and 269 matched healthy undergraduate controls. The polymorphisms of eight tag single nucleotide polymorphisms (SNPs) on the COMT gene were tested using polymerase chain reaction (PCR)-based Ligase Detection Reaction (PCR-LDR). The eight tag SNPs on the COMT gene assessed were not associated with neurotic disorders. Our finding suggests that the COMT gene may not be a susceptibility gene for neurotic disorders.

To investigate the association ofMETSNPs with gender disparity in thyroid tumors, as well as the metastasis and prognosis of patients, 858 patients with papillary thyroid carcinoma (PTC), 556 patients with nodular goiter, and 896 population-based normal controls were recruited. The genotyping ofMETSNPs was carried out using the Sequenom MassARRAY system. The distribution ofMETSNPs (rs1621 and rs6566) was different among groups. Gender stratification analysis revealed a significant association between the rs1621 genotype and PTC in female patients (P=0.037), but not in male patients (P>0.05). For female patients, the rs1621 AG genotype was significantly higher in patients with PTC than in normal controls (P=0.01) and revealed an increasing risk of PTC (OR: 1.465, 95% CI: 1.118–1.92). However, association analysis of the rs1621 genotype with metastasis and prognosis revealed no significant correlation in both male and female patients. The findings of our study showed that polymorphism of SNP locus rs1621 inMETgene may be associated with gender disparity in PTC. Higher AG genotypes in rs1621 were correlated with PTC in female patients, but not in male patients.

BACKGROUND Zinc finger protein 259 (ZNF259) binds to the cytoplasmic domain of epidermal growth factor receptor (EGFR) in quiescent cells and contributes tolipid metabolism. This case and control study investigated the association between ZNF259 single nucleotide polymorphisms (SNPs) and metabolic syndrome (MetS). METHODS This study included 1,812 MetS patients and 2,036 controls from the Jilin province of Northeastern China. MetS was diagnosed using the International Diabetes Federation (IDF) criteria. Three ZNF259 SNPs (rs964184, rs2075290 and rs2075294) were genotyped using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS). RESULTS There were significant differences between metabolic syndrome and healthy control subjects for the ZNF259 rs964184 and rs2075290 genotypes. The minor alleles of both SNPs were associated with an increased risk of MetS and associated conditions (elevated triglycerides, elevated blood pressure, increased abdominal obesity, fasting hyperglycemia, and low HDL-C; p < 0.05). The distribution of haplotype G-G-G (rs964184, rs2075290 and rs2075294) was significantly different between MetS patients and controls (OR = 1.39; 95% CI, 1.24 - 1.56; p < 0.01). CONCLUSIONS This study demonstrated that ZNF259 variants were associated with elevated MetS risk in a Han Chinese population from the Jilin province of Northeastern China.

This cross-sectional survey among Chinese university students aimed to estimate the prevalence and risk factors of major depressive disorder (MDD) among undergraduates, in order to provide basic information for the prevention and treatment of depression among the college-aged population.A total of 2,046 undergraduates were interviewed face to face using the World Health Organization Composite International Diagnostic Interview Version 3.0 (WHO-CIDI, version 3.0). Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria were used to diagnose MDD. Logistic regression was used to evaluate the associations between MDD and selected correlates.The survey response rate was 90.1% (N = 1,843). The prevalence rates of MDD were 3.9% (lifetime), 2.4% (12 months) and 0.4% (30 days). No significant gender or age differences were found in prevalence rates. No sociodemographic characteristics were related to the lifetime prevalence of MDD. In contrast, family structure and environment factors specifically being from a single-parent family (odds ratio [OR] = 2.513, confidence interval [CI] = 1.404-2.500), parents having mental problems (OR = 1.809, CI = 1.104-2.964), and physical punishment (OR = 1.789, CI = 1.077-3.001) were associated with higher lifetime prevalence of MDD.These findings showed a relatively lower prevalence of DSM-IV/CIDI MDD in this sample of Chinese undergraduates than that reported for students in other countries. However, the prevalence rate for university students was higher than that reported for general Chinese population. Family structure and socio-environmental factors in the student's family of origin significantly correlated with the lifetime prevalence of MDD.

This study investigates the genetic association between methyl-CpG-binding domain (MBD) gene polymorphisms and schizophrenia. A total of 200 family trios consisting of fathers, mothers, and affected offspring with schizophrenia were recruited as our participants. Four tag SNPs on MBD1 (rs125555, rs140689, rs140687, and rs140686), three tag SNPs on MBD2 (rs3876254, rs7614, and rs1145317), and three tag SNPs on MBD3 (rs7252741, rs4807934, and rs4807122) genes were tested using the PCR-based ligase detection reaction (PCR-LDR). The transmission disequilibrium test showed that rs1145317 on the MBD2 gene was significantly overtransmitted from parents to schizophrenic offspring (P=0.026). The haplotype-based haplotype relative risk test revealed that the haplotype rs7614-rs1145317 (A-G) was associated with schizophrenia (P=0.029). Our finding suggests that the MBD2 gene may be a susceptibility gene for schizophrenia.

Ataxia telangiectasia mutated (ATM) gene is critical in the process of recognizing and repairing DNA lesions and is related to invasion and metastasis of malignancy. The incidence rate of papillary thyroid cancer (PTC) has increased for several decades and is higher in females than males. In this study, we want to investigate whether ATM polymorphisms are associated with gender-specific metastasis of PTC. 358 PTC patients in Northern China, including 109 males and 249 females, were included in our study. Four ATM single nucleotide polymorphisms (SNPs) were genotyped using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS). Association between genotypes and the gender-specific risk of metastasis was assessed by odds ratios (OR) and 95% confidence intervals (CI) under the unconditional logistic regression analysis. Significant associations were observed between rs189037 and metastasis of PTC in females under different models of inheritance (codominant model:OR=0.15, 95% CI 0.04–0.56,P=0.01for GA versus GG andOR=0.08, 95% CI 0.01–0.74,P=0.03for AA versus GG, resp.; dominant model:OR=0.49, 95% CI 0.25–0.98,P=0.04; overdominant model:OR=0.47, 95% CI 0.25–0.89,P=0.02). However, no association remained significant after Bonferroni correction. Our findings suggest a possible association between ATM rs189037 polymorphisms and metastasis in female PTCs.

The present study detected three single nucleotide polymorphisms (SNPs), BanISNP at the PLA2G4A locus, rs1648833 at the PLA2G4B locus, and rs1549637 at the PLA2G4C locus, to investigate a genetic association between the cytosolic PLA2 (cPLA2) genes and schizophrenia. A total of 240 Chinese parent–offspring trios of Han descent were recruited for the genetic analysis. The transmission disequilibrium test (TDT) showed allelic association for rs1549637 (χ2 = 5.68, uncorrected P = 0.017), but not for BanISNP and rs1648833. The conditioning on genotype (COG) test revealed a disease association for the BanISNP–rs1648833 combination (χ2 = 12.54, df = 3, P = 0.0057) and for the BanISNP–rs1549637 combination (χ2 = 9.72, df = 2, P = 0.021), but the conditioning on allele (COA) test did not show such an association for the above two combinations. Neither the COA test nor the COG showed a disease association for the rs1648833–rs1549637 combination. In the combination of all three SNPs, the COG test, but not the COA test, showed a strong association (χ2 = 22.93, df = 6, P = 0.0008). These findings suggest that these three cPLA2 genes may all be involved in contributing to the etiology of schizophrenia although their effect size appears to be relatively small. © 2005 Wiley-Liss, Inc.

Abnormal phospholipid metabolism in the brain plays an important role in neuropsychiatric diseases. Phospholipase A2 is crucial for maintaining normal neuro-physiological function. The aim of this study was to investigate the association between polymorphisms of the membrane-associated calcium-independent phospholipase A2 gamma (PNPLA8) gene and schizophrenia in Han Chinese in north China. The PCR-based ligase detection reaction was applied to detect 3 single nucleotide polymorphisms (SNPs) in the PNPLA8 gene among 201 Chinese pedigrees. The genotypic frequency of the PNPLA8 polymorphisms did not deviate from the Hardy-Weinberg equilibrium both in affected offspring and parental groups. Haploid relative risk (HRR) and transmission disequilibrium tests (TDT) showed that the 3 SNPs were not associated with schizophrenia (p>0.05), but further analysis with TDT showed that the rs40876 polymorphism was associated with schizophrenia in males (χ2=4.667, p=0.031). Our data suggest that rs40876 in PNPLA8 may be associated with schizophrenia in males.

Diagnosis of schizophrenia does not have a clear objective test at present, so we aimed to identify the potential biomarkers for the diagnosis of schizophrenia by comparison of serum protein profiling between first-episode schizophrenia patients and healthy controls. The combination of a magnetic bead separation system with matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF-MS) was used to analyze the serum protein spectra of 286 first-episode patients with schizophrenia, 41 chronic disease patients and 304 healthy controls. FlexAnlysis 3.0 and ClinProTools(TM) 2.1 software was used to establish a diagnostic model for schizophrenia. The results demonstrated that 10 fragmented peptides demonstrated an optimal discriminatory performance. Among these fragmented peptides, the peptide with m/z 1206.58 was identified as a fragment of fibrinopeptide A. Receiver operating characteristic analysis for m/z 1206.58 showed that the area under the curve was 0.981 for schizophrenia vs healthy controls, and 0.999 for schizophrenia vs other chronic disease controls. From our result, we consider that the analysis of serum protein spectrum using the magnetic bead separation system and MALDI-TOF/TOF-MS is an objective diagnostic tool. We conclude that fibrinopeptide A has the potential to be a biomarker for diagnosis of schizophrenia. This protein may also help to elucidate schizophrenia disease pathogenesis.

Papillary thyroid carcinoma (PTC) is one of the most common tumors of the thyroid gland. The common risk factors of PTC include ionizing radiation, positive family history, and thyroid nodular disease. PTC was identified in Europeans by conducting a genome-wide association study, and a strong association signal with PTC was observed in rs944289 and NKX2-1 (located at the 14q13.3 locus), which was probably the genetic risk factor of PTC. This study aimed to examine the association of this gene with PTC in Chinese. A total of 354 patients with PTC and 360 healthy control subjects from the Han population of Northern China were recruited in the study. These individuals were genotyped to determine rs12589672, rs12894724, rs2076751, and rs944289. The association of rs944289 with PTC was obtained (C vs. T, P = 0.027, OR = 1.264, 95% CI = 1.026 - 1.557; and C/C - C/T vs. T/T, P = 0.034, OR = 1.474, 95% CI = 1.028 - 2.112). Conducting a subgroup analysis, we found a marginal difference in the allele frequency distribution of rs944289 (adjusted P = 0.062) between the patients with PTC and multi-nodular goiter and the control subjects. We also observed an interaction (P = 0.029; OR = 2.578, 95% CI = 1.104 - 6.023) between rs944289 and diabetes in patients with PTC. In conclusion, rs944289 was associated with an increased risk of PTC in the Han population of Northern China, but no clear association was observed in either of the tag single nucleotide polymorphisms of NKX2-1.

To explore the association between histone deacetylase-2 (HDAC2) and histone deacetylase-3 (HDAC3) gene polymorphisms and schizophrenia.A total of 208 family trios consisting of fathers, mothers and affected offspring with schizophrenia were recruited as our subjects. Four tag SNPs on HDAC2 (rs10499080, rs6568819, rs2499618 and rs13204445) and two tag SNPs on HDAC3 (rs11741808, rs2530223) genes were selected. The Mass ARRAY Assay Design software (Sequenom) was used to design amplification and allele specific extension primers. The Hardy-Weinberg equilibrium (HWE) for genotypic distributions was tested using the chi-square goodness-of-fit test. Allelic association for a single tag SNP was analyzed by using family-based association tests including the haplotype-based haplotype relative risk (HHRR) test and the transmission disequilibrium test (TDT).The genotypic distributions of HDAC2 SNPs rs6568819, rs2499618 and rs13204445 and HDAC3 SNPs rs11741808 and rs2530223 were all in Hardy-Weinberg equilibrium (P0.05). HHRR analysis revealed no associations between the SNPs and schizophrenia (P0.05). In addition, the TDT did not show any significant associations between HDAC2 and HDAC3 SNPs and schizophrenia (P0.05).HDAC2 and HDAC3 might not be associated with schizophrenia in the Chinese population.

To investigate the association between the polymorphisms of fatty acid desaturase 1 ( FADS1 ), fatty acid desaturase 2 ( FADS2 ) and elongation of very long chain fatty acids like 2 ( ELOVL2 ) gene and coronary artery disease (CAD) in a Chinese Han population. Three single nucleotide polymorphisms (SNPs) from these genes were genotyped using PCR-based restriction fragment length polymorphism analysis in 199 CAD cases and 192 controls of Han Chinese origin. rs174556 in the FADS1 gene showed allelic ( P= 0.002) and genotypic ( P= 0.030) association with the disease, while there was no disease association for the other two SNPs. The frequency of rs174556 minor allele (T) was significantly higher in the case group than the control group. The trans phase gene–gene interaction analysis showed that the combined genotype of rs174556 (T/T) and rs3756963 (T/T) was weakly associated with the disease ( P= 0.043). rs174556 in the FADS1 gene is very likely to be associated with CAD in the Chinese Han population.

To investigate an association between gene polymorphisms of FADS 1 (fatty acid desaturase 1) , FADS2 (fatty acid desaturase 2) and ELOVL2 (elongation of very long chain fatty acids (FEN1/ Elo2, SUR4/Elo3, yeast) -like 2) and paranoid schizophrenia of the Han ethnicity in Jilin province of China.We genotyped 3 single nucleotide polymorphisms from 3 candidate genes in 100 paranoid schizophrenia cases and 95 healthy controls using polymerase chain reaction-restriction fragment length polymorphism method. All samples are from Han ethnicity in Jilin province of China.The genotype distributions of rs174556 in FADS1 gene and rs174617 in FADS2 gene showed no significant difference between case and control groups (P0.05). The genotype distribution of rs3756963 in ELOVL2 gene showed significant difference between case group and control group (P0.05). The distribution proportion of allele T carriers in case group was higher than that in control group. Trans-phase gene interaction analysis showed that the distribution proportion of combined genotypes included rs3756963 (T/T) was higher in case group than that in control group (P0.05).rs174556 in FADS1 gene and rs174617 in FADS2 gene may not be associated with paranoid schizophrenia. rs3756963 in ELOVL2 gene may be associated with paranoid schizophrenia.

To study the prevalence and risk factors of neurotic disorders (NDs) among Chinese university students. Stratified random sampling was used to select students who were interviewed using the World Health Organization Composite International Diagnostic Interview Version 3.0 to diagnose psychiatric disorder and collected socio-demographic, and family structure and environment data. The response rate was 90 % (N = 1,843). The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) criteria were used to diagnose NDs. We used logistical regression to evaluate the links between NDs and selected correlates. The prevalence of NDs was 25.6 % (lifetime), 15.7 % (12-month), and 6.8 % (30-day) among the university students with no significant gender differences in these rates. No family structure characteristics were related to 12-month prevalence of NDs (P > 0.05). In contrast, family environment factors including a history of family disputes (OR 1.562, CI 1.108–2.203), parental mental health problems (OR 1.800, CI 1.379–2.349), and absence of care in childhood (OR 1.916, 95 % CI 1.331–2.759) were associated with higher prevalence rates of NDs. Our findings show a high prevalence of NDs in this sample of Chinese undergraduates. Social environment factors, in the student’s family of orientation, were significantly associated with the prevalence of NDs. These findings support the importance of negative family experiences during childhood and adolescence and increasing vulnerability to NDs.

In order to investigate the potential mechanisms in troglitazone-induced apoptosis in HT29 cells, the effects of PPARγ and POX-induced ROS were explored.[3- (4, 5)-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay, Annexin V and PI staining using FACS, plasmid transfection, ROS formation detected by DCFH staining, RNA interference, RT-PCRRT-QPCR, and Western blotting analyses were employed to investigate the apoptotic effect of troglitazone and the potential role of PPARγ pathway and POX-induced ROS formation in HT29 cells.Troglitazone was found to inhibit the growth of HT29 cells by induction of apoptosis. During this process, mitochondria related pathways including ROS formation, POX expression and cytochrome c release increased, which were inhibited by pretreatment with GW9662, a specific antagonist of PPARγ. These results illustrated that POX upregulation and ROS formation in apoptosis induced by troglitazone was modulated in PPARγ-dependent pattern. Furthermore, the inhibition of ROS and apoptosis after POX siRNA used in troglitazone-treated HT29 cells indicated that POX be essential in the ROS formation and PPARγ-dependent apoptosis induced by troglitazone.The findings from this study showed that troglitazone-induced apoptosis was mediated by POX-induced ROS formation, at least partly, via PPARγ activation.

Background Analyses of large scale psychiatric epidemiology surveys suggest that common mental disorders can be generalized into two underlying dimensions, internalizing disorders (e.g. depression, and anxiety) and externalizing disorders (e.g. addictions). The present study explores the interactions among the genes (SLC6A4, BDNF, and MAOA) and selected environment factors (G × E), and gene × gene (G × G) interactions for internalizing disorders in the sample of Chinese university students. Methods This is a genetic case control study. 259 undergraduates affected with internalizing disorders and 269 healthy controls were included. Multiple logistic regression was used to explore the potential environmental risk factors. G × E interactions were analyzed using the method developed by Mukherjee et al. (2008). Analyses of G × G interactions were conducted by generalized multifactor dimensionality reduction (GMDR) (Lou et al., 2007). We have previously reported on the polymorphism information for ten single nucleotide polymorphisms (SNPs) on SLC6A4, BDNF, and MAOA genes (Meng et al., 2009; Meng, 2010). Results We found that an offspring's reported parents' negative mood, subject's unwillingness to express emotion, being an only child, having an unfulfilling relationship with his/her mother, and increased activity and behavior restrictions by his/her father were social environment risk factors for internalizing disorders. No statistically significant interactions were found in the G × E analyses. G × G analyses found that subjects with mutational alleles concurrently on rs10835210 and rs2030324 (BDNF gene) were significantly likely to develop internalizing disorders. Those with one mutated allele on either SNPs were 1.761 times, and those with both mutated alleles were 3.353 times, more likely to develop internalizing disorders. Conclusion A negative family emotional environment was found to be associated with internalizing disorders. BDNF gene variants were also found to be similarly associated. Using conservative statistical analyses we did not find any G × E interactions.