Olanzapine-induced weight gain is associated with the |[minus]|759C|[sol]|T and |[minus]|697G|[sol]|C polymorphisms of the HTR2C gene

Weight gain, a serious problem associated with some antipsychotic drugs, notably olanzapine and clozapine, was suggested to be associated with −759C/T polymorphism of the 5-HT2C receptor gene. This study aimed to examine a potential association of two functional polymorphisms of the promoter region of this gene: −759C/T (rs3813929) and −697G/C (rs518147), with weight gain after 6 weeks of olanzapine monotherapy. It included 107 patients with schizophrenia; among them 36 are first-episode drug-naïve patients. Analysis was carried out by PCR–restriction fragment length polymorphism. A protective effect of −759T and −697C alleles was found: significantly less patients with −697C (3/51) and no patient with −759T (0/28) alleles experienced body mass index increase 10% (P=0.0006 and 0.002, respectively). The same was true for drug-naïve patients possessing any of the variant alleles. There was a significant association of haplotypes with a 10% body mass index increase (P=0.001). On the basis of the additional statistical analysis, the more important role of −697C allele was suggested.