Drnovsek Eva, Jensterle Mojca, Goričar Katja, Redenšek Sara, Janež Andrej, Milsisav Irina, Dolžan Vita
Faculty of Medicine, University of Ljubljana, Slovenia.
Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia.
Arch Med Sci. 2022 Jun 30;20(6):1993-2001. doi: 10.5114/aoms/150867. eCollection 2024.
Cholecystokinin (CCK) is involved in several metabolic pathways, and CCK agonists are considered as a 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 ( and , respectively) may modify their biological actions, we investigated the impact of and genetic variability on anthropometric and metabolic parameters in patients with PCOS.
Our cross-sectional study included 168 patients with PCOS and 82 healthy female controls genotyped for polymorphisms in (rs6448456 and rs1800857) and (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 a larger waist circumference ( = 0.027) and more visceral fat ( = 0.046). Among PCOS patients, carriers of at least one polymorphic rs6448456 C allele had significantly higher total blood cholesterol and LDL, and significantly lower blood glucose levels after 30, 60 and 90 min of the oral glucose tolerance test (all < 0.05). Healthy controls with at least one polymorphic CCKAR rs1800857 C allele were less likely to have a high metabolic syndrome burden ( = 0.029).
Genetic variability in affects lipid profile and post-load glucose levels in patients with PCOS and is associated with metabolic syndrome burden in healthy young women. Further investigation of the role of genetic variability in and could contribute to development of individually tailored treatment strategies with CCK receptor agonists.
胆囊收缩素（CCK）参与多种代谢途径，CCK激动剂被认为是代谢风险增加人群（包括多囊卵巢综合征（PCOS）患者）潜在的新型治疗选择。由于胆囊收缩素A和B受体基因（分别为CCKAR和CCKBR）的遗传变异可能会改变其生物学作用，我们研究了CCKAR和CCKBR基因变异对PCOS患者人体测量和代谢参数的影响。
我们的横断面研究纳入了168例PCOS患者和82例健康女性对照，对其CCKAR基因（rs6448456和rs1800857）和CCKBR基因（rs2929180、rs1800843、rs1042047和rs1042048）的多态性进行基因分型。
所研究的多态性与PCOS患者的人体测量特征无关。然而，在健康对照中，至少携带一个CCKBR rs1800843多态性等位基因的携带者腰围更大（P = 0.027）且内脏脂肪更多（P = 0.046）。在PCOS患者中，至少携带一个CCKAR rs6448456 C多态性等位基因的携带者总血胆固醇和低密度脂蛋白显著更高，口服葡萄糖耐量试验30、60和90分钟后的血糖水平显著更低（均P < 0.05）。至少携带一个CCKAR rs1800857 C多态性等位基因的健康对照患高代谢综合征负担的可能性更小（P = 0.029）。
CCKAR基因变异影响PCOS患者的血脂谱和负荷后血糖水平，并与健康年轻女性的代谢综合征负担相关。进一步研究CCKAR和CCKBR基因变异的作用可能有助于开发CCK受体激动剂的个体化治疗策略。
