UCP2 and CFH Gene Variants with Genetic Susceptibility to Schizophrenia in Turkish Population.

OBJECTIVE: Schizophrenia (Sch) is a complex, multifactorial psychiatric disorder. Growing evidence shows that oxidative damage and immunological dysfunction exist in the Sch physiopathology. In the present study, we aimed to evaluate whether the Uncoupling protein 2 and Complement factor H gene variants play any role in susceptibility to Sch. METHODS: This study was carried out on 200 individuals (100 Sch patients and 100 healthy controls). Genomic DNA was extracted from blood samples. UCP2-866G /A (rs659366) and CFHY402H variants were analyzed by PCR-RFLP analysis. RESULTS: The UCP2 -866G/A variant G/G genotype and G allele were associated significantly with increased risk of Sch (p=0.001, p=0.001, respectively). The subjects were carrying UCP2 -866G/A variant G/G genotype had 4.377-fold increased risk for Sch. There was no significant difference between the groups for the genotype and allele frequencies of the CFH Y402H variant (p>0.05). The observed genotype counts deviated significantly from those expected in Sch patients according to the HWE for UCP2 -866G/A variant (p=0.001). CONCLUSION: We present the first results investigating UCP2 -866G/A/ and CFH Y402H variants for susceptibility to Sch in a Turkish population. These results indicate that the UCP2 -866G/A, but not CFH Y402H variant, might play an important role in the development of Sch.

Effect of monoamine oxidase B A644G variant on nicotine dependence and/or schizophrenia risk

Abstract Objectives Schizophrenia (Sch) is a severe and chronic mental illness. Smoking prevalence is higher in patients with Sch than general population. We aimed to investigate the effects of MAOB gene A644G variant on nicotine dependence (ND) and Sch+ND risk in Turkish population and to evaluate by bioinformatic analysis. Methods Present study included 161 individuals with ND, 223 patients with Sch+ND, and 96 non-smoker controls. MAOB A644G variant was analyzed using PCR-RFLP method. As the MAOB gene is located on the X chromosome, each gender was analysed separately. Results The total distributions of AA, AG and GG genotypes of MAOB gene A644G were 44.7%, 22.4% and 32.9% in the ND group, 45.3%, 25.1% and 29.6% in the Sch+ND group and, 44.8, 22.9% and 32.3% in non-smoker controls. No significant differences were observed between groups for the MAOB A644G genotype and allele frequencies when female group compared to male group (p > 0.05). Examination of disease associations of SNPs from each miRNA gene region in GWAS databases yielded results for aging, bipolar disorder, autoimmune, and neurological diseases. Discussion Our results indicate that the MAOB gene A644G variant is not associated with ND and/or Sch susceptibility in the Turkish population.

Dopamine D4 Receptor Gene Exon III VNTR Variant Influences Smoking Status in Turkish Population.

INTRODUCTION: Dopaminergic gene variants may affect nicotine dependence through their possible impact on the dopamine reward pathway. The purpose of this study is to investigate the relationship between the variable number tandem repeat (VNTR) variant in exon III of the Dopamine D4 receptor (DRD4) gene and genetic predisposition of smoking status in a Turkish population. METHODS: We performed a study comparing 154 subjects as the smoker group, and 111 subjects as the non-smoker group. Genotyping for the DRD4 VNTR variant was performed using a PCR method. RESULTS: There was a significant difference between smoker and non-smoker groups regarding the distribution of the alleles and genotypes of the DRD4 gene (p=0.000, p=0.000, respectively). The 2R allele was higher in the non-smoker group compare to the smoker group (p=0.000). We found that the 2/7 and 4/9 genotypes were more common in smokers than non-smoker group (p=0.037, p=0.028, respectively) while 2/4 genotype was more prevalent in non-smokers than smokers (p=0.000). When the number of repeat alleles (48 bp) are accepted as short (S) if six or less, and as long (L) if seven or more, it was found that the frequency of S/S genotype of the DRD4 VNTR variant was lower in the smoker group and S/L genotype was higher in the smoker group (p=0.006, p=0.006, respectively). The subjects carrying the S/L genotype have a 2.25-fold increased risk for smoking than a non-smoker. CONCLUSION: The results indicated that the subjects carrying DRD4 exon III VNTR S/L genotype have a risk for smoking status in a Turkish population.

XRCC4 rs6869366 polymorphism is associated with susceptibility to both nicotine dependence and/or schizophrenia

Abstract Background: Oxidative stress induced DNA damage has been assumed to contribute to the etiopathogenesis of schizophrenia (Sch). Smoking prevalence was more common in patients with Sch. The X-ray repair cross-complementation group 4 (XRCC4) gene plays an important role in the repair of DNA double-strand breaks. Objective: The purpose of this study was to investigate whether XRCC4 rs6869366 polymorphism has a relationship both in nicotine dependence (ND) and Sch+ND risk. Methods: One hundred and four patients with Sch+ND, 133 subjects with ND only and 70 healthy controls were enrolled in the study. XRCC4 rs6869366 polymorphism was analyzed using PCR-RFLP assay. Results: The frequency of XRCC4 rs6869366 GG genotype was more common in the ND and Sch+ND group than controls (p = 0.001 and p = 0.001, respectively). XRCC4 rs6869366 TT genotype was lower in both ND and Sch+ND group compared to controls (p = 0.001 and p = 0.001, respectively). Also, XRCC4 rs6869366 G allele was higher in Sch+ND group than controls (p = 0.001) while XRCC4 rs6869366 T allele was lower in ND group than healthy controls (p=0.001). XRCC4 rs6869366 GT genotype was lower in ND group than control group (p = 0.003). Discussion: These results suggested that the XRCC4 rs6869366 polymorphism G related genotype/allele was associated with susceptibility to both ND and Sch+ND in a Turkish population.