Role of leptin and 5-HT2C receptor gene in risperidone-induced obesity

Objective: To assess the changes of body weight and biochemical indicators related to metabolic process in subjects with schizophrenia after risperidone therapy and to analyze the association of leptin gene -2548G/A polymorphism and 5-HT2C receptor gene -759C/T polymorphism with the above-mentioned changes. Methods: A total of 123 patients with schizophrenia were treated with risperidone for 10 weeks. Their body weight, waistline and body mass index (BMI) were measured on admission and every 2 weeks subsequently; biochemical indicators including fasting plasma glucose, fasting blood concentration of lipid and leptin were also measured on admission, 4-week and 10-week treatment. The polymorphisms of leptin gene -2548G/A and 5-HT2C receptor gene -759C/T were determined by PCR-RFLP in patients so as to compare these biochemical indicators between different genotypes. Results: After 10 weeks' risperdone treatment, the patients' body weight, waistline, BMI and fasting plasma glucose increased significantly (P<0.001); blood plasma leptin increased significantly (P=0.013) in the fourth treatment week. So did fasting blood concentration of lipid-cholesterol and LDL (P=0.004). In addition, the increase of blood plasma leptin was closely correlated (R=0.219, P=0.029) with body weight and BMI; however, all the above-mentioned changes were not significantly correlated with the distribution of genotypes (P>0.05). Conclusion: During the preliminary stage of risperidone treatment, subjects have substantial weight gain as well as increases in the level of fasting plasma glucose, fasting blood concentration of lipid and blood plasma leptin. The -2548G/A polymorphism in promoter region of leptin gene and the -759C/T polymorphism in promoter region of 5-HT2C receptor gene are not associated with risperidone-induced weight gain, disorder of fasting blood concentration of lipid, fasting plasma glucose, or blood plasma leptin.