Gene-gene interactions of suicidal behavior by multifactor dimensionality reduction analysis :Do both 5-HT and GAD1 work? / 西安交通大学学报(医学版)

Objective To investigate gene-gene interactions of suicidal behavior with single-nucleotide-polymorphism (SNP) in MAOA ,GAD1 and 5-HTR2C by multifactor dimensionality reduction .Methods For this case-control study ,six SNPs were captured in related genes and detected in blood samples obtained from 21 patients with suicidal behavior and 50 healthy individuals .The genotype frequency and allele frequency as well as the Hardy-Weinberg equilibrium (HWE) ,tests were performed and compared by plink software .The gene-gene interactions models were built by the MDR software .Results The HWE test for case group showed that rs3813928 rs518147 of 5-HTR2C gene was not in line with HWE ( P< 0 .05) .However ,the additive model analysis after adjustment by gender indicated that the polymorphism had a positive correlation with suicidal behavior in case group .The case and control groups differed significantly only in genotype frequencies of 5-HTR2C gene (χ2 =6 .18 , P=0 .04) .There was no significant difference in allele and genotype frequencies of the other genes ( P>0 .05) .The best combination model of MDR was rs5953210-rs769391 OR=20 .19 ,95% CI 4 .19-97 .38 , P<0 .01 ,with significant interaction . Conclusion The 5-HTR2C gene rs3813928 and rs518147 polymorphisms may play an important role in the susceptibility to suicidal behavior .The combination of MAOA with GAD1 has a significant interaction which may increase the risk of suicidal behavior .

Association between serotonin 2C receptor gene (HTR2C) polymorphisms and psychopathological symptoms in children and adolescents

Serotonin 2C receptors (5HT2C) are involved in serotonin-driven dynamic equilibrium adjustments responsible for homeostatic stability in brain structures that modulate behavior and emotions. Single nucleotide polymorphisms (SNPs) from the serotonin 2C receptor gene (HTR2C) have been associated with several neurological and mental disorders, including abnormalities in cognitive and emotional processes. The aim of this study was to evaluate the association between the rs6318 SNP of the HTR2C gene and behavioral characteristics exhibited by children and adolescents based on the Child Behavior Checklist (CBCL/6-18) inventory. Eighty-five psychiatric outpatients between 8 and 18 years of age underwent genotyping of the rs6318 SNP. The CBCL/6-18 scale was administered to their caregivers. The chi-squared test was used to assess differences in the frequency of C and G alleles of the rs6318 SNP relative to the grouped CBCL/6-18 scores; significance level was 5%. The presence of the G allele of rs6318 was found to be associated with characteristics of aggressive behavior and social problems, and aggressive behavior was found to be associated with heterozygosis in females. These findings contribute to the identification of mental and behavioral phenotypes associated with gene expression.

Genetic Polymorphisms in the HTR2C and Peroxisome Proliferator-Activated Receptors Are Not Associated with Metabolic Syndrome in Patients with Schizophrenia Taking Clozapine

OBJECTIVE: Genetic variation in the serotonin-2C receptor encoded by the HTR2C gene is one of the genetic determinants of antipsychotic-induced weight gain. Peroxisome proliferator-activated receptors are nuclear receptors regulating the expression of genes involved in lipid and glucose metabolism. In this cross-sectional study, we investigated whether HTR2C-759C/T, HTR2C-697G/C, PPARalpha V227A, and PPARgamma 161C/T genotypes were associated with metabolic syndrome (MetS) in patients with schizophrenia taking clozapine. METHODS: One hundred forty-six Korean patients using clozapine for more than one year were genotyped for the HTR2C-759C/T, HTR2C-697G/C, PPARalpha V227A, and PPARgamma 161C/T polymorphisms, and their weight, waist circumference, blood pressure, triglycerides, high-density lipoprotein-cholesterol, total cholesterol, and glucose were measured. We used the criteria for MetS proposed by the National Cholesterol Education Program-adapted Adult Treatment Panel III. RESULTS: The prevalence of MetS was 47.3% and was similar among men (49%) and women (42.9%). We found no significant differences between patients with and without MetS in terms of genotypes or allele frequencies. Logistic regression analyses also revealed no association between MetS and each genotype. CONCLUSION: We did not find significant associations between four polymorphisms (HTR2C-759C/T, HTR2C-697G/C, PPARalpha V227A, and PPARgamma 161C/T) and MetS in patients with schizophrenia taking clozapine.

Genetic predictors of antipsychotic-induced weight gain: a case-matched multi-gene study / 中南大学学报(医学版)

Objective To determine associations between weight gain induced by antipsychotic and the polymorphisms of HTR2C gene -759C/T and -697G/C,histamine-1 receptor gene,leptine gene -2548G/A,and adiponectin gene +276G/T and +45T/G.Methods In the casematched study,85 patients who gained more than 7％ of their pre-drug body weight served as the study group and another 85 patients who gained less than 7％ of their pre-drug body weight served as the control group.The ligation diction reaction technique was used to analyze the frequencies of the -759C/T and -697G/C polymorphism of the HTR2C gene,-2548A/G polymorphism of leptin gene,+ 276G/T and + 45T/G polymorphism of adiponectin gene and glu349asp polymorphism of H1 receptor gene.Results The presence of the -759C allele,-697G allele,-2548A allele and + 276G allele was significantly higher in the study group than that in the control group (P ＜ 0.05 ).Conclusion The -759C/T and -697G/C polymorphisms of the promoter region of 5HT2C receptor gene,-2548A/G polymorphisms of leptin gene and + 276G/T polymorphisms of adiponectin gene may be associated with the antipsychotic induced weight gain.The glu349asp polymorphisms of histamine-1 receptor gene is not associated with antipsychotic induced weight gain.