Olanzapine-induced weight gain is associated with the-759C/T and-697G/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-naive 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-naive 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. The Pharmacogenomics Journal (2009) 9, 234-241; doi: 10.1038/tpj.2009.18; published online 12 May 2009