Effect of 5-HT2C receptor gene polymorphism (HTR2C-759C/T) on metabolic adverse effects in Thai psychiatric patients treated with risperidone

Background: The use of Atypical antipsychotics (AAPs) is related to metabolic disturbances, which put psychiatric patients at risk for cardiovascular morbidity and mortality. Evidence is emerging of genetic risk factors. The HTR2C gene is an essential candidate in pharmacogenetic studies of antipsychotic-induced metabolic effects. Nevertheless, there were inconsistent results among studies.

Objective: To investigate the relationship between -759C/T, functional polymorphism of the HTR2C gene and metabolic adverse effects in Thai psychiatric patients treated with risperidone monotherapy.

Method: In this cross-sectional study, 108 psychiatric patients treated with risperidone monotherapy for ≥3 months were recruited. Anthropometric measurements and laboratory tests were obtained upon enrollment and history of treatment was reviewed from medical records. Weight gain was defined as an increase ≥7% of baseline weight. Metabolic syndrome was evaluated according to the 2005 International Diabetes Federation (IDF) Asia criteria. The -759C/T, polymorphism was genotyped. The associations between -759C/T polymorphism and metabolic side effects were analyzed. Multiple logistic regression was used for determining potential confounders.

Results: Neither weight gain nor metabolic syndrome was significantly associated with -759C/T allelic and genotype variants of HTR2C. However, T allele of -759C/T polymorphism significantly associated with the hypertension. This association was not affected by possible confounding factors such as gender, risperidone dose, duration of treatment and family history of hypertension.

Conclusion: Our findings suggest that psychiatric patients with T allele of -759C/T polymorphism may be at higher risk for hypertension. Further study with prospective design with larger patient groups are needed.