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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.

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.

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.

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.

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.

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.

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.

Objective The present study investigated the prevalence and risk factors for Metabolic syndrome. We evaluated the association between single nucleotide polymorphisms (SNPs) in the apolipoprotein APOA1/C3/A4/A5 gene cluster and the MetS risk and analyzed the interactions of environmental factors and APOA1/C3/A4/A5 gene cluster polymorphisms with MetS. Methods A study on the prevalence and risk factors for MetS was conducted using data from a large cross-sectional survey representative of the population of Jilin Province situated in northeastern China. A total of 16,831 participations were randomly chosen by multistage stratified cluster sampling of residents aged from 18 to 79 years in all nine administrative areas of the province. Environmental factors associated with MetS were examined using univariate and multivariate logistic regression analyses based on the weighted sample data. A sub-sample of 1813 survey subjects who met the criteria for MetS patients and 2037 controls from this case-control study were used to evaluate the association between SNPs and MetS risk. Genomic DNA was extracted from peripheral blood lymphocytes, and SNP genotyping was determined by MALDI-TOF-MS. The associations between SNPs and MetS were examined using a case-control study design. The interactions of environmental factors and APOA1/C3/A4/A5 gene cluster polymorphisms with MetS were assessed using multivariate logistic regression analysis. Results The overall adjusted prevalence of MetS was 32.86% in Jilin province. The prevalence of MetS in men was 36.64%, which was significantly higher than the prevalence in women (29.66%). MetS was more common in urban areas (33.86%) than in rural areas (31.80%). The prevalence of MetS significantly increased with age (OR = 8.621, 95%CI = 6.594–11.272). Mental labor (OR = 1.098, 95%CI = 1.008–1.195), current smoking (OR = 1.259, 95%CI = 1.108–1.429), excess salt intake (OR = 1.252, 95%CI = 1.149–1.363), and a fruit and dairy intake less than 2 servings a week were positively associated with MetS (P

The present study was designed to detect three single nucleotide polymorphisms (SNPs) located on 22q11 that was thought as being of particularly importance for genetic research into schizophrenia. We recruited a total of 176 Chinese family trios of Han descent, consisting of mothers, fathers and affected offspring with schizophrenia for the genetic analysis. The transmission disequilibrium test (TDT) showed that of three SNPs, rs10314 in the 3′-untranslated region of the CLDN5 locus was associated with schizophrenia (χ2= 4.75,P= 0.029). The other two SNPs, rs1548359 present in the CDC45L locus centromeric of rs10314 and rs739371 in the 5′-flanking region of the CLDN5 locus, did not show such an association. The global chi-square (χ2) test showed that the 3-SNP haplotype system was not associated with schizophrenia although the 1-df test for individual haplotypes showed that the rs1548359(C)-rs10314(G)-rs739371(C) haplotype was excessively non-transmitted (χ2= 5.32,P= 0.02). Because the claudin proteins are a major component for barrier-forming tight junctions that could play a crucial role in response to changing natural, physiological and pathological conditions, the CLDN5 association with schizophrenia may be an important clue leading to look into a meeting point of genetic and environmental factors.