Association between HTR2C polymorphisms and metabolic syndrome in patients with schizophrenia treated with atypical antipsychotics

BackgroundPrevious research indicates that common single-nucleotide polymorphisms (SNPs) in the serotonin 5-HT2C receptor gene (HTR2C) are associated with metabolic syndrome (MetS) related to antipsychotic treatment. This study analyzes a large sample of patients with schizophrenia treated with atypical antipsychotics to determine whether variation in the HTR2C is associated with MetS.MethodsSix tag SNPs, capturing all common genetic variations in the HTR2C gene in the Han population, were genotyped in 456 Chinese schizophrenic inpatients treated with atypical antipsychotics (clozapine: 171, olanzapine: 91, and risperidone: 194).ResultsSingle-marker based analysis shows that of the six HTR2C SNPs, the rs498177 SNP showed a significant association with MetS in female patients, and the C allele was associated with an increased risk of MetS (for genotype TT/TC/CC: MetS vs. non-MetS = 50%/27%/23% vs. 69%/28%/3%, and for allele T/C: MetS vs. non-MetS = 63%/37% vs. 83%/17%, p = 0.0007). Haplotype analysis shows that the A–C type of rs521018–rs498177 in the HTR2C gene significantly decreased the risk of MetS (corrected p = 0.0108) in female patients.ConclusionsThe results of this study support the role of HTR2C genetic variants in susceptibility to MetS in patients treated with atypical antipsychotics. However, this association is gender-dependent.