The findings suggest interacting genetic risk factors and smoking influence development of metabolic syndrome in patients on antipsychotic drugs.

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Genetic factors contribute to the individual variability in weight gain caused by several antipsychotic drugs. The FTO gene is associated with obesity in the general population; we have investigated whether a common risk polymorphism (rs9939609) in this gene is associated with antipsychotic drug-induced weight gain and obesity. Two samples were studied: (1) 93 first-episode patients receiving antipsychotic drugs for the first time and having body weight monitored for up to 12 months; (2) 187 chronic patients with schizophrenia assessed for measures of obesity and metabolic dysfunction. No association of FTO genotype with weight gain was found in initially drug-naive patients. The chronically treated patients had a significant association of genotype with body mass index (BMI), reflected in associations with waist circumference, waist:hip ratio and the frequency of central obesity. These findings indicate that FTO genotype has a major effect on body weight determined by BMI in chronically treated patients with schizophrenia.

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