Association study of polymorphisms in cholecystokinin gene and its receptors with antipsychotic induced weight gain in schizophrenia patients

Cholecystokinin (CCK) gene and its receptors play an important role in several biological processes including satiety signaling. Administration of exogenous or endogenously secreted CCK leads to decreased food intake in both rats and humans. Similarly, in rats pretreated with intraperitoneal CCK, antagonists of the CCKA receptor prevent decrease in food intake. The CCKB receptor plays an important role in anxiety and gastric acid secretion.We investigated the role of polymorphisms in the CCK gene (2 SNPs) and its receptors CCKA (4 SNPs) and CCKB (4SNPs, 1 microsatellite, CTn) in antipsychotic induced weight gain (n = 215). Weight change (%) from baseline was compared across genotypic groups using analysis of covariance.In the European ancestry patients treated with clozapine or olanzapine a trend of association was observed with the SNP rs2929183 (p = 0.10) in CCKBR gene. Carriers of the genotype AA (3.23% ± 4.8) gained less weight than the AG and GG genotypes (6.50% ± 6.5; p = 0.035). A similar trend was observed for the CTn repeat, where carriers of the LL genotype gained less weight (3.73% ± 5.41) than the S allele carrying genotypes (6.29% ± 6.2, p = 0.05). In the subjects of African ancestry we observed similar marginal association although with the opposite allele. However, none of these observations would survive corrections for multiple testing. None of the other polymorphisms in either CCK or CCKA receptor genes was associated with weight change (%).In conclusion, CCKB receptor gene may play a role in antipsychotic induced weight gain. However, these observations need to be replicated in a larger and independent sample set.

Research Highlights
► Cholecystokinin gene and its receptors are important for satiety signaling.
► Administration of exogenous or endogenously secreted CCK leads to decreased food intake.
► Polymorphisms in the CCK gene and its receptors CCKA and CCKB were investigated for possible association with antipsychotic induced weight gain.
► A trend for association was observed with CTn repeat and rs2929183 in CCKBR gene.
► CCKB receptor gene may play a role in antipsychotic induced weight gain.