Association Analysis Of 5-hydroxytryptamine 2C Receptor Gene Polymorphisms And Schizophrenia With Type 2 Diabetes Mellitus

Background and Objective:Schizophrenia?SCZ?is one of the most debilitating neuropsychiatric disorders,affecting an estimated 1%of the adult population worldwide.Its pathomechanism is unknown,although current evidence supports the idea that interactions between environmental and genetic factors contribute to disease development.Atypical antipsychotics?AAPs?act on glucose and lipid metabolism,they may cause insulin resistance which leading to high FPG,and gradually develop into type 2 diabetes mellitus?T₂DM?.SCZ and T₂DM are heterogeneous?multi-factor?disease with genetic predisposition.Studies on 5-HTR_2CC gene indicate that it may be a candidate gene of AAPs metabolic side effects.The effect of Clozapine on glucose metabolism is more significant,and mainly target on 5-HTR_2CC to ameliorate psychotic symptoms.Therefore,the present study was to investigate 5-HTR_2CC gene polymorphisms correlation in SCZ with T₂DM and its relevance with the metabolism of Chinese Han population.Subjects and Methods:This study selected long-term SCZ in-patients with or without T₂DM intervened by clozapine?257 cases,288 cases?,T₂DM patients group?207 cases?and normal control group?329 cases?.Use Taqman genotyping technology to type tag SNP of 5-HTR_2CC gene with allele,genotype and haplotype frequency,to compare the difference between each groups and the correlation between SNPs with metabolic indicators.Results:1)There was a significant difference in genotype frequencies of rs498177??²=17.1,P=0.0002?between SCZ and the normal control group;there was not a difference in the frequency distribution of rs498177 genotype?P=0.053?between the T₂DM group and the normal control group.2)The frequency distribution of Haplotype GT?rs2192371,rs5988072?between combined group and the SCZ group was statistical significant??²=7.592,P=0.0048?.3)Stratified analysis on 3 SNP loci genotype of 5-HTR2c gene showed:the difference of FPG levels in AA,AG and GG genotype of rs2192371 locus carriers was statistically significant?F=2.735,P=0.042?and the AA genotype was significantly higher than AG genotype?P=0.006?.Conclusions:The present study provided suggestive evidence that the rs498177 was significantly correlated with schizophrenia in Chinese Han population.Haplotype GT?rs2192371,rs5988072?of 5-HTR_2CC gene was significantly related to the type 2 diabetes mellitus in Chinese Han population with schizophrenia and the AA genotype of 5-HTR_2CC gene rs2192371 locus was significantly correlated with FPG level.