Investigation of melanocortin system gene variants in antipsychotic-induced weight gain

Objectives. The use of second-generation antipsychotic medications may result in substantial weight gain in a subset of schizophrenia patients. Distinct populations of neurons expressed in the hypothalamus, including the cocaine-and amphetamine-regulated transcript (CART), the polypeptide pro-opiomelanocortin (POMC) and the agouti-related protein (AGRP), have regulatory roles in weight control and energy homeostasis. Thus, we investigated the potential role of CART, POMC and AGRP genetic variants in antipsychotic-induced weight gain (AIWG). Methods. Five CART single nucleotide polymorphisms (SNPs) (rs10515115, rs3763153, rs3857384, rs11575893, rs16871471), three POMC SNPs (rs6713532, rs1047521, rs3754860) and one AGRP SNP (rs1338993), were genotyped in 218 patients treated with antipsychotics for chronic schizophrenia and evaluated for AIWG. We compared weight change (%) across genotypic groups using analysis of covariance. Results. None of the SNPs in POMC, CART, AGRP were significantly associated with AIWG in the refined samples stratified by ethnicity and medication treatment. Conclusions. In this exploratory study, we observed that POMC, CART and AGRP gene variants are not a major contributor to AIWG. However larger samples are required to completely rule out their effect on AIWG.