Cholecystokinin (CCK) is involved in several metabolic pathways and CCK agonist are considered as potential novel treatment option in populations with increased metabolic risk, including polycystic ovary syndrome (PCOS). As genetic variability of cholecystokinin A and B receptor genes (CCKAR and CCKBR, respectively) may modify its biological actions, we investigated the impact of CCKAR and CCKBR genetic variability on anthropometric and metabolic parameters in patients with PCOS.

Material and methods:
Our cross-sectional study included 168 patients with PCOS and 82 healthy female controls genotyped for polymorphisms in CCKAR (rs6448456 and rs1800857) and CCKBR (rs2929180, rs1800843, rs1042047 and rs1042048) genes.

The investigated polymorphisms were not associated with anthropometric characteristics of patients with PCOS, however, among healthy controls carriers of at least one polymorphic CCKBR rs1800843 allele had bigger waist circumference (p=0.027) and more visceral fat (p=0.046). Among PCOS patients carriers of at least one polymorphic CCKAR rs6448456 C allele had significantly higher total blood cholesterol and LDL, and significantly lower blood glucose levels after 30, 60 and 90 minutes of the oral glucose tolerance test (all p<0.05). Healthy controls with at least one polymorphic CCKAR rs1800857 C allele were less likely to have high metabolic syndrome burden (p=0.029).

Genetic variability in CCKAR affects lipid profile and post-load glucose levels in patients with PCOS and is associated with metabolic sydrome burden in healthy young women. Further investigation of the role of genetic variability in CCKAR and CCKBR could contribute to development of individually tailored treatment strategies with CCK receptor agonists.

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