BDNF rs6265 methylation and genotype interact on risk for schizophrenia

Epigenetic mechanisms can mediate gene-environment interactions relevant for complex disorders. The BDNF gene is crucial for development and brain plasticity, is sensitive to environmental stressors, such as hypoxia, and harbors the functional SNP rs6265 (Val⁶⁶Met), which creates or abolishes a CpG dinucleotide for DNA methylation. We found that methylation at the BDNF rs6265 Val allele in peripheral blood of healthy subjects is associated with hypoxia-related early life events (hOCs) and intermediate phenotypes for schizophrenia in a distinctive manner, depending on rs6265 genotype: in ValVal individuals increased methylation is associated with exposure to hOCs and impaired working memory (WM) accuracy, while the opposite is true for ValMet subjects. Also, rs6265 methylation and hOCs interact in modulating WM-related prefrontal activity, another intermediate phenotype for schizophrenia, with an analogous opposite direction in the 2 genotypes. Consistently, rs6265 methylation has a different association with schizophrenia risk in ValVals and ValMets. The relationships of methylation with BDNF levels and of genotype with BHLHB2 binding likely contribute to these opposite effects of methylation. We conclude that BDNF rs6265 methylation interacts with genotype to bridge early environmental exposures to adult phenotypes, relevant for schizophrenia. The study of epigenetic changes in regions containing genetic variation relevant for human diseases may have beneficial implications for the understanding of how genes are actually translated into phenotypes.     

Influence of the 5-HT3A Receptor Gene Polymorphism and Childhood Sexual Trauma on Central Serotonin Activity

Background

Gene-environment interactions are important for understanding alterations in human brain function. The loudness dependence of auditory evoked potential (LDAEP) is known to reflect central serotonergic activity. Single nucleotide polymorphisms (SNPs) in the 5-HT3A serotonin receptor gene are associated with psychiatric disorders. This study aimed to investigate the effect between 5-HT3A receptor gene polymorphisms and childhood sexual trauma on the LDAEP as an electrophysiological marker in healthy subjects.

Methods

A total of 206 healthy subjects were recruited and evaluated using the childhood trauma questionnaire (CTQ) and hospital anxiety and depression scale (HADS). Peak-to-peak N1/P2 was measured at five stimulus intensities, and the LDAEP was calculated as the linear-regression slope. In addition, the rs1062613 SNPs of 5-HT3A (CC, CT, and TT) were analyzed in healthy subjects.

Results

There was a significant interaction between scores on the CTQ-sexual abuse subscale and 5-HT3A genotype on the LDAEP. Subjects with the CC polymorphism had a significantly higher LDEAP than T carriers in the sexually abused group. In addition, CC genotype subjects in the sexually abused group showed a significantly higher LDAEP compared with CC genotype subjects in the non-sexually abused group.

Conclusions

Our findings suggest that people with the CC polymorphism of the 5-HT3A gene have a greater risk of developing mental health problems if they have experienced childhood sexual abuse, possibly due to low central serotonin activity. Conversely, the T polymorphism may be protective against any central serotonergic changes following childhood sexual trauma.     

BDNF genotype is associated with hippocampal volume in mild traumatic brain injury

The negative long‐term effects of mild traumatic brain injury (mTBI) have been a growing concern in recent years, with accumulating evidence suggesting that mTBI combined with additional vulnerability factors may induce neurodegenerative‐type changes in the brain. However, the factors instantiating risk for neurodegenerative disease following mTBI are unknown. This study examined the link between mTBI and brain‐derived neurotrophic factor (BDNF) genotype, which has previously been shown to regulate processes involved in neurodegeneration including synaptic plasticity and facilitation of neural survival through its expression. Specifically, we examined nine BDNF single‐nucleotide polymorphisms (SNPs; rs908867, rs11030094, rs6265, rs10501087, rs1157659, rs1491850, rs11030107, rs7127507 and rs12273363) previously associated with brain atrophy or memory deficits in mTBI. Participants were 165 white, non‐Hispanic Iraq and Afghanistan war veterans between the ages of 19 and 58, 110 of whom had at least one mTBI in their lifetime. Results showed that the BDNF SNP rs1157659 interacted with mTBI to predict hippocampal volume. Furthermore, exploratory analysis of functional resting state data showed that rs1157659 minor allele homozygotes with a history of mTBI had reduced functional connectivity in the default mode network compared to major allele homozygotes and heterozygotes. Apolipoprotein E (APOE) was not a significant predictor of hippocampal volume or functional connectivity. These results suggest that rs1157659 minor allele homozygotes may be at greater risk for neurodegeneration after exposure to mTBI and provide further evidence for a potential role for BDNF in regulating neural processes following mTBI.     

Meta-analysis of the association between five single nucleotide polymorphisms in the <Emphasis Type="Italic">BDNF</Emphasis> gene and allergic inflammation susceptibility

The association between five single nucleotide polymorphisms (SNPs) in brain-derived neurotrophic factor (BDNF) gene (rs6265, rs10767664, rs12273539, rs962369 and rs11030101) and allergic inflammatory disease susceptibility has been extensively reported, while the conclusions were inconclusive. The present study was designed to qualitatively and quantitatively evaluate the relationship between the BDNF polymorphisms and allergic disease risks. A comprehensive literature search of the shared public electronic databases was conducted before September 1, 2016. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using review manager 5.3. Eleven eligible studies (a total of 5217, 6432, 6432, 6432, 4216 subjects focused on rs6265, rs10767664, rs12273539, rs962369 and rs11030101, respectively) were finally contained. Significant genetic association of rs6265 variant and susceptibility of allergic inflammation was observed under allele contrast, recessive and over-dominant model in the overall analysis. Besides, stratified analysis by ethnicity found that the close relationship between rs6265 polymorphism and increased allergic disease risk of Caucasian was observed under recessive and over-dominant model, as well as under allele contrast, recessive, homozygous and over-dominant model in the Asian. Additionally, subgroup analysis based on the disease types showed the obvious relation of rs6265 and asthma risk in several hereditary model. Moreover, strong association between rs10767664 polymorphism and extraordinary risk of allergic disease was also detected in four genetic models. However, no association was discovered with rs962369, rs12273539 and rs11030101. The present meta-analysis suggested that the SNPs (rs10767664 and rs6265) in the BDNF gene is potentially associated with increased allergic disease susceptibility.     

HLA-DP Polymorphisms Affect the Outcomes of Chronic Hepatitis B Virus Infections,Possibly through Interacting with Viral Mutations

Genetic polymorphisms of HLA-DP have been associated with hepatitis B virus (HBV) persistence. We aimed to determine the effect of HLA-DP polymorphisms on the generation of HBV mutations and their interactions on the outcomes of HBV infection. rs3077, rs3135021, rs9277535, and rs2281388 were genotyped in 1,342 healthy controls, 327 HBV clearance subjects, and 2,736 HBV-positive subjects, including 1,108 hepatocellular carcinoma (HCC) patients, using quantitative PCR. HBV mutations were determined by sequencing. Multiplicative interactions of HLA-DP polymorphisms and viral mutations were assessed by multivariate logistic regression. rs3077 (from subjects with genotype CT combined with those from subjects with genotype TT [CT+TT] versus CC), rs3135021 (GA+AA versus GG), rs9277535 (GA+AA versus GG), and rs2281388 (CC versus CT+TT) significantly decreased HBV persistence. This effect was found only in genotype B HBV-infected subjects compared to HBV clearance subjects. HLA-DP polymorphisms promoting HBV clearance were associated with a lower prevalence of mutations increasing HCC risk (C1653T, T1674C/G, A1846T, G1896A and pre-S2 mutations and pre-S deletion in genotype C) and a higher prevalence of mutations decreasing HCC risk (G1652A, T1673C, T1674C, G1719T, G1730C, and G1799C in genotype B and A1727T in genotype C). Significant effects of viral mutations on cirrhosis and HCC were selectively evident in those with HLA-DP polymorphisms promoting HBV persistence. The interactions of C1653T, T1674C/G, and G1896A mutations with HLA-DP polymorphisms promoting HBV clearance significantly decreased cirrhosis risk. The interaction of rs9277535 AA with the T1674C/G or G1719T mutation in genotype C significantly decreased HCC risk. In conclusion, HLA-DP polymorphisms affect genotype B HBV clearance, regulate immune selection of viral mutations, and influence cirrhosis and HCC risks contributed by HBV mutations.     

Association of rs6265 and rs2030324 Polymorphisms in Brain-Derived Neurotrophic Factor Gene with Alzheimer’s Disease: A Meta-Analysis

Background

The association between polymorphisms rs6265 and rs2030324 in brain-derived neurotrophic factor (BDNF) and Alzheimer’s disease (AD) has been widely reported, but the results remain controversial.

Methods

A comprehensive search of Pubmed, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Med Online and China Biology Medical literature database (CBM) was performed. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed or random-effects models. We excluded the studies with OR>3.0 or OR<0.3 for sensitive analysis. Subgroup analysis by ethnicity, form of AD and gender was carried out. Meta-regression was conducted to explore the potential sources of between-study heterogeneity.

Results

29 articles with 7548 cases and 7334 controls concerning rs6265 and 22 articles with 5796 cases and 5706 controls concerning rs2030324 were included in this meta-analysis. The combined evidence suggested rs6265 contributing significantly to the increased risk of AD in females (codominant: fixed-effects model (FEM): OR = 1.13, 95% CI = 1.04–1.23; dominant: FEM: OR = 1.17, 95% CI = 1.05–1.31), especially for Caucasian females (codominant: FEM: OR = 1.18, 95% CI = 1.03–1.34; dominant: FEM: OR = 1.18, 95% CI = 1.01–1.37) and female late-onset Alzheimer’s disease (LOAD) patients (codominant: FEM: OR = 1.22, 95% CI = 1.05–1.41; dominant: FEM: OR = 1.23, 95% CI = 1.03–1.46). No evidence indicated an association between rs2030324 with AD in codominant (random-effects model (REM): OR = 1.06, 95% CI = 0.89–1.26) and dominant (REM: OR = 1.05, 95% CI = 0.86–1.27) models.

Conclusion

This meta-analysis suggested A allele of rs6265 might increase the risk of AD in Caucasian females and female LOAD patients. In addition, no evidence indicated an association between rs2030324 with AD. Further studies are needed to confirm these results.     

Brain-derived neurotrophic factor and risk of schizophrenia: an association study and meta-analysis

Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the central nervous system (CNS), and performs many biological functions such as neural survival, differentiation, and plasticity. Previous studies have suggested that variants in the BDNF gene increase the risk of schizophrenia. In this study, we genotyped one (GT)n dinucleotide repeat and three SNPs (rs6265, rs2030324, and rs2883187) in a Chinese sample (617 cases and 672 controls). In addition, we performed an updated meta-analysis based on 16 population-based case-control studies examining association between rs6265 and schizophrenia. In single-locus analysis, no significant association was found between BDNF polymorphisms and schizophrenia in our subjects. The meta-analysis based on Asian and Caucasian subjects did not give positive result that rs6265 is associated with schizophrenia. However, haplotype analysis found a common four-locus haplotype is protective against schizophrenia (Case 3.1% vs Control 7%, p=0.0011). Our data provides evidence that BDNF is a susceptibility gene for schizophrenia in Chinese subjects.     

An obesity genetic risk score is associated with metabolic syndrome in Chinese children

Recent genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with body mass index (BMI)/obesity. In this study, we aim to examine the associations of obesity related loci with risk of metabolic syndrome (MetS) in a children population from China. A total of 431 children with MetS and 3046 controls were identified based on the modified ATPIII definition. 11 SNPs (FTO rs9939609, MC4R rs17782313, GNPDA2 rs10938397, BDNF rs6265, FAIM2 rs7138803, NPC1 rs1805081, SEC16B rs10913469, SH2B1 rs4788102, PCSK1rs6235, KCTD15 rs29941, BAT2 rs2844479) were genotyped by TaqMan 7900. Of 11 SNPs, GNPDA2 rs10938397, BDNF rs6265, and FAIM2 rs7138803 were nominally associated with risk of MetS (GNPDA2 rs10938397: odds ratio (OR) = 1.21, 95% confidence interval (CI) = 1.04–1.40, P = 0.016; BDNF rs6265: OR = 1.19, 95% CI = 1.03–1.39, P = 0.021; FAIM2 rs7138803: OR = 1.20, 95% CI = 1.02–1.40, P = 0.025); genetic risk score (GRS) was significantly associated with risk of MetS (OR = 1.09, 95% CI = 1.04–1.15, P = 5.26 × 10^− 4). After further adjustment for BMI, none of SNPs were associated with risk of MetS (all P > 0.05); the association between GRS and risk of MetS remained nominally (OR = 1.02, 95%CI = 0.96–1.08, P = 0.557). However, after correction for multiple testing, only GRS was statistically associated with risk of MetS in the model without adjustment for BMI. The present study demonstrated that there were nominal associations of GNPDA2 rs10938397, BDNF rs6265, and FAIM2 rs7138803 with risk of MetS. The SNPs in combination have a significant effect on risk of MetS among Chinese children. These associations above were mediated by adiposity.     

Functional rs6265 polymorphism in the brain-derived neurotrophic factor gene confers protection against neurocognitive dysfunction in posttraumatic stress disorder among Chinese patients with hepatocellular carcinoma

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that plagues trauma survivors. Evidence shows that brain-derived neurotrophic factor (BDNF) may be involved in the occurrence and development of PTSD. Here we tried to demonstrate whether BDNF gene polymorphisms are correlated with neurocognitive function following PTSD in patients with hepatocellular carcinoma (HCC). This study included 102 patients with HCC complicated with PTSD, 146 HCC patients, and 152 healthy volunteers. Initially, we evaluated the neurocognitive function of the study subjects. Next, we measured BDNF G11757C and rs6265 polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. The correlation of BDNF polymorphisms and BDNF level with HCC complicated with PTSD was evaluated. The results revealed that HCC complicated with PTSD showed decreased serum BDNF level and Mini-mental state examination (MMSE) score. Serum BDNF level of HCC and HCC complicated with PTSD was positively correlated with MMSE score. GA + AA allele and A allele of rs6265 increased the risk of PTSD among patients with HCC. GA and AA genotypes of rs6265 were correlated with the decreased MMSE score of HCC complicated with PTSD. Haplotype GA of rs6265 and G11757C increased the risk of PTSD for HCC, while haplotype CG decreased this risk. Lastly, the logistic regression analysis suggested that low BDNF level was a contributor to HCC complicated with PTSD, while GG genotype of rs6265 served as a protective factor. Collectively, this study defines the GG genotype of BDNF rs6265 polymorphism as a protector to HCC complicated with PTSD. In addition, these results provided a promising target for PTSD prevention in patients with HCC.     

Combined effects of the BDNF rs6265 (Val66Met) polymorphism and environment risk factors on psoriasis vulgaris

Smoking, alcohol consumption and higher body mass index (BMI) are well established risk factors for psoriasis and also associated with the clinical traits of the disease. And the genetic influences on these three risk factors indeed exist. Previously studies have demonstrated these risk factors related genetic variants may also play a role in the development of risk factors-related diseases. Then we performed a hospital-based study in order to evaluate the combined effect of the risk factors and their related polymorphism rs6265 in brain-derived neurotrophic factor (BDNF) gene on psoriasis vulgaris (PV) risk and clinic traits. The case–control study involved 660 subjects including 345 cases and 315 controls in Chinese Han population. The variant of rs6265 was typed by SNaPshot Multiplex Kit (Applied Biosystems Co., USA). We confirmed that higher BMI (≥25), smoking and alcohol consumption were risk factors for PV, and the estimated ORs were 1.63(95 % confidence interval (CI); 1.12–2.37), 2.09(95 % CI; 1.44–3.03) and 1.65(95 % CI; 1.15–2.37) respectively. Genotype and allele distributions did not differ significantly between case and control. However, we found combined effect of rs6265 genotype (GG) and higher BMI (≥25) increased risk of PV (OR = 2.09; 95 % CI, 1.02–4.28; P < 0.05; adjusted OR = 3.19; 95 % CI, 1.37–7.45; P < 0.05) and clinically severity of PV (OR = 2.71; 95 % CI, 1.09–6.72; P < 0.05; adjusted OR = 1.25; 95 % CI, 1.10–1.40; P < 0.05). But none such significant combined effect was observed between others genotype (AA and AG) and other risk factors. In conclusions, the combined effect of BDNF rs6265 genotype (GG) and higher BMI may increases the risk and clinical severity of PV in Chinese Han population.     

TLR9 -1486T/C and 2848C/T SNPs Are Associated with Human Cytomegalovirus Infection in Infants

Toll-like receptor 9 (TLR9) recognizes non-methylated viral CpG-containing DNA and serves as a pattern recognition receptor that signals the presence of human cytomegalovirus (HCMV). Here, we present the genotype distribution of single-nucleotide polymorphisms (SNPs) of the TLR9 gene in infants and the relationship between TLR9 polymorphisms and HCMV infection. Four polymorphisms (-1237T/C, rs5743836; -1486T/C, rs187084; 1174G/A, rs352139; and 2848C/T, rs352140) in the TLR9 gene were genotyped in 72 infants with symptomatic HCMV infection and 70 healthy individuals. SNP genotyping was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Digested fragments were separated and identified by capillary electrophoresis. The HCMV DNA copy number was measured by a quantitative real-time PCR assay. We found an increased frequency of heterozygous genotypes TLR9 -1486T/C and 2848C/T in infants with HCMV infection compared with uninfected cases. Heterozygous variants of these two SNPs increased the risk of HCMV disease in children (P = 0.044 and P = 0.029, respectively). In infants with a mutation present in at least one allele of -1486T/C and 2848C/T SNPs, a trend towards increased risk of cytomegaly was confirmed after Bonferroni’s correction for multiple testing (Pc = 0.063). The rs352139 GG genotype showed a significantly reduced relative risk for HCMV infection (Pc = 0.006). In contrast, the -1237T/C SNP was not related to viral infection. We found no evidence for linkage disequilibrium with the four examined TLR9 SNPs. The findings suggest that the TLR9 -1486T/C and 2848C/T polymorphisms could be a genetic risk factor for the development of HCMV disease.     

Polymorphisms of two histamine-metabolizing enzymes genes and childhood allergic asthma: a case control study

Background

Histamine-metabolizing enzymes (N-methyltransferase and amiloride binding protein 1) are responsible for histamine degradation, a biogenic amine involved in allergic inflammation. Genetic variants of HNMT and ABP1 genes were found to be associated with altered enzyme activity. We hypothesized that alleles leading to decreased enzyme activity and, therefore, decreased inactivation of histamine may be responsible for altered susceptibility to asthma.

Methods

The aim of this study was to analyze polymorphisms within the HNMT and ABP1 genes in the group of 149 asthmatic children and in the group of 156 healthy children. The genetic analysis involved four polymorphisms of the HNMT gene: rs2071048 (-1637T/C), rs11569723 (-411C/T), rs1801105 (Thr105Ile = 314C/T) and rs1050891 (1097A/T) and rs1049793 (His645Asp) polymorphism for ABP1 gene. Genotyping was performed with use of PCR-RFLP. Statistical analysis was performed using Statistica software; linkage disequilibrium analysis was done with use of Haploview software.

Results

We found an association of TT genotype and T allele of Thr105Ile polymorphism of HNMT gene with asthma. For other polymorphisms for HNMT and ABP1 genes, we have not observed relationship with asthma although the statistical power for some SNPs might not have been sufficient to detect an association. In linkage disequilibrium analysis, moderate linkage was found between -1637C/T and -411C/T polymorphisms of HNMT gene. However, no significant differences in haplotype frequencies were found between the group of the patients and the control group.

Conclusions

Our results indicate modifying influence of histamine N-methyltransferase functional polymorphism on the risk of asthma. The other HNMT polymorphisms and ABP1 functional polymorphism seem unlikely to affect the risk of asthma.     

Polymorphic variant at the IL2 region is associated with type 1 diabetes and may affect serum levels of interleukin-2

Polymorphic variants at the interleukin-2 (IL2) locus affect the risk of several autoimmune disorders. Our aim was to evaluate the association of the four IL2 polymorphisms (rs6822844, rs6534349, rs2069762 and rs3136534) with type 1 diabetes (T1D) in the Polish population, and to correlate them with the serum interleukin-2 levels. 543 unrelated T1D patients and 706 healthy control subjects were enrolled. The minor T allele at rs6822844 was significantly less frequent in T1D compared to controls (p = 0.002; OR 0.71; 95 % CI 0.571–0.880). Likewise, the frequency of the TT genotype was decreased among the affected individuals (p = 0.007). In healthy subjects, stratification according to the rs6822844 genotype revealed significant differences in circulating interleukin-2 (p = 0.037) with the highest levels in TT protective genotypes. Three other IL2 polymorphisms did not display significant differences in allele and genotype distribution. In conclusion, the rs6822844 variant is associated with T1D and may play a functional role, or reflect the influence of another causative genetic variant in linkage disequilibrium.     

BDNF Val66Met Polymorphism Is Associated with Self-Reported Empathy

Empathy is an important driver of human social behaviors and presents genetic roots that have been studied in neuroimaging using the intermediate phenotype approach. Notably, the Val66Met polymorphism of the Brain-derived neurotrophic factor (BDNF) gene has been identified as a potential target in neuroimaging studies based on its influence on emotion perception and social cognition, but its impact on self-reported empathy has never been documented. Using a neurogenetic approach, we investigated the association between the BDNF Val66Met polymorphism and self-reported empathy (Davis’ Interpersonal Reactivity Index; IRI) in a sample of 110 young adults. Our results indicate that the BDNF genotype is significantly associated with the linear combination of the four facets of the IRI, one of the most widely used self-reported empathy questionnaire. Crucially, the effect of BDNF Val66Met goes beyond the variance explained by two polymorphisms of the oxytocin transporter gene previously associated with empathy and its neural underpinnings (OXTR rs53576 and rs2254298). These results represent the first evidence suggesting a link between the BDNF gene and self-reported empathy and warrant further studies of this polymorphism due to its potential clinical significance.     

Brain‐derived neurotrophic factor genotype is associated with brain gray and white matter tissue volumes recovery in abstinent alcohol‐dependent individuals

Neuroimaging studies have linked the methionine (Met) allele of the brain‐derived neurotrophic factor (BDNF) gene to abnormal regional brain volumes in several psychiatric and neurodegenerative diseases. However, no neuroimaging studies assessed the effects of this allele on brain morphology in alcohol use disorders and its demonstrated change during abstinence from alcohol. Here we assessed the effects of the BDNF Val66Met (rs6265) polymorphism on regional brain tissue volumes and their recovery during short‐term abstinence in treatment‐seeking alcohol‐dependent individuals. 3D T1 weighted magnetic resonance images from 62 individuals were acquired at 1.5 T at one week of abstinence from alcohol; 41 of the participants were rescanned at 5 weeks of abstinence. The images were segmented into gray matter (GM), white matter (WM) and cerebrospinal fluid and parcellated into regional volumes. The BDNF genotype was determined from blood samples using the TaqMan technique. Alcohol‐dependent Val (Valine)/Met heterozygotes and Val homozygotes had similar regional brain volumes at either time point. However, Val homozygotes had significant GM volume increases, while Val/Met heterozygotes increased predominantly in WM volumes over the scan interval. Longitudinal increases in GM but not WM volumes were related to improvements in neurocognitive measures during abstinence. The findings suggest that functionally significant brain tissue volume recovery during abstinence from alcohol is influenced by BDNF genotype.     

No association between the G196A and C270T polymorphism of the brain-derived neurotrophic factor gene and male infertility

Brain-derived neurotrophic factor (BDNF) plays important roles in neuronal development and reproductive action. Abnormal expression of BDNF gene has been detected in human sperm and seminal serum. In the present study, we investigated the possible association of G196A and C270T polymorphism of BDNF gene with male infertility. The genotypes of the G196A and C270T polymorphisms were in Hardy-Weinberg equilibrium both in fertile and infertile group. The genotype distribution frequencies were similar between infertile and fertile group. The results showed that the G196A and C270T polymorphism of the BDNF gene is unrelated to the male infertility, at least in a Chinese population.     

Association of SLC18A1, TPH1, and RELN gene polymorphisms with risk of paranoid schizophrenia

A biochip was developed to examine the polymorphisms of genes associated with schizophrenia risk, including DISC1, RELN, ZNF804A, PLXNA2, COMT, SLC18A1, CACNA1C, ANK2, TPH1, PLAA, and SNAP-25. Allele and genotype frequencies of the genes were determined in 198 schizophrenics and 192 healthy subjects from Bashkortostan (ethnic Russians and Tatars). The frequencies of allele A (p = 0.007) and genotype AA (p = 0.002) of the rs2270641 A>C polymorphism of SLC18A1 in the patients with paranoid schizophrenia was lower than in the healthy subjects. The frequency of genotype AA of the rs1800532 C>A polymorphism of TPH1 in the schizophrenics was higher than in the healthy subjects (p = 0.036). Compared with the healthy subjects, the ethnic Tatar patients with paranoid schizophrenia had a lower frequency of allele C of the rs7341475 C>T polymorphism of RELN (p = 0.039) and a higher frequency of genotype AA of the rs1800532 C>A polymorphism of TPH1 (p = 0.019, OR = 2.52, CI 1.18-5.38). The frequency of allele C (p = 0.0001) and genotype GC (p = 0.0001) of the rs1327175 G>C polymorphism of PLXNA2 was elevated in the patients with a family history of paranoid schizophrenia. Based on the results, the SLC18A1, TPH1, and RELN polymorphisms were associated with risk of schizophrenia.     

Association of insulinase gene polymorphisms with type 2 diabetes mellitus in patients from the Moscow population

Association of 13 single nucleotide polymorphisms (SNPs) of insulinase (IDE) gene with type 2 diabetes mellitus (T2D) in the Moscow population has been examined. Three polymorphic markers (rs7078413, rs7899603, and rs551266) associated with the risk of T2D development have been revealed. Allele and genotype frequency distribution for these three markers differed significantly only in the sample of females between T2D patients and control individuals, while only in case of rs7078413 SNP genotype frequencies varied significantly in the total population.     

Human leukocyte antigen (HLA)-C polymorphisms are associated with a decreased risk of rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune rheumatological disease thought to have substantial genetic contributions. Several genetic factors involved in the susceptibility to psoriasis and psoriatic arthritis (PsA) have been identified with genome-wide association studies, including human leukocyte antigen (HLA)-C, junction adhesion molecule 2 (JAM2) and REL. Psoriasis and PsA may share many features in common with RA. We hypothesized that this polymorphism may contribute to RA susceptibility in a Chinese population. We studied HLA-C rs10484554 C/T, HLA-C rs12212594 T/C, HLA-C rs12191877 C/T, JAM2 rs2829866 A/T and REL rs702873 G/A polymorphisms in 520 patients with RA and 520 controls in a Chinese population. HLA-C rs12191877 C/T polymorphism was in complete linkage disequilibrium (LD) (D′ = 1.0, r ² = 1.0) with HLA-C rs10484554 C/T polymorphism. When the HLA-C rs10484554 CC homozygote genotype was used as the reference group, the TT/CT genotypes were associated with a significantly decreased risk for RA (adjusted OR = 0.72, 95 % CI = 0.52–0.99, p = 0.044). We found that the HLA-C rs12191877 C/T polymorphism was also associated with a decreased risk of RA. HLA-C rs12212594 T/C, JAM2 rs2829866 A/T and REL rs702873 G/A polymorphisms were not associated with the risk of RA. These results provide evidence that HLA-C polymorphisms are associated with a decreased risk of RA.     

Influences of −482C&gt;T and 3238G&gt;C polymorphisms of the <Emphasis Type="Italic">Apolipoprotein C3</Emphasis> gene on prevalence of metabolic syndrome

Apolipoprotein C3 (ApoC3) plays a regulatory role in triglyceride (TG) metabolism. The higher level of TG can be a cause in pathogenesis of the vascular diseases or metabolic syndrome (MetS). In this study, we examined the associations of ApoC3 polymorphisms (?482C>T rs2854117 and 3238G>C rs5128) with Korean MetS patients. A total of 835 subjects were investigated, including 320 patients with MetS and 515 healthy subjects. The genotype analysis of the ApoC3 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism methods. Of the two polymorphisms studied, we observed a significant difference in the ?482C>T polymorphism between the MetS and control groups. The TT genotype of the ?482C>T polymorphism was associated with increased risk for MetS, compared with the controls (OR 1.627, 95 % CI 1.075–2.463, P = 0.021). The association was female-specific. No associations were found for the risk of MetS in the 3238G>C polymorphism. Haplotypes composed of two polymorphisms, however, were associated with MetS susceptibility in only male group. The 3238G>C polymorphism was significantly associated with TG levels (P = 0.013). Our data suggest that the ApoC3 ?482C>T polymorphism is associated with increased MetS susceptibility in the Korean population.