Selected CNR1 polymorphisms and hyperandrogenemia as well as fat mass and fat distribution in women with polycystic ovary syndrome

Abstract

The endocannabinoid system is postulated to play an important role in the etiology of obesity, insulin resistance, fat distribution and metabolic disorders. Insulin resistance associated with abdominal obesity plays a leading role in the etiology of hyperandrogenism and other clinical features of the polycystic ovary syndrome (PCOS). A total of 174 women 16–38 years old, diagnosed with PCOS according to the Rotterdam criteria are recruited. Control group consisted of 125 healthy women 18–45 years old. Medical history, physical examination, anthropometric parameters and metabolic parameters were carried out. Six CNR1 gene polymorphisms were diagnosed. We observed a significantly three times higher risk of GG genotype in the polymorphism rs12720071 in women with PCOS versus the control group (p = 0.0344, OR = 3.01). A similar, significant 8-fold higher risk (p = 0.0176, OR = 8.81) was demonstrated for genotype CC polymorphism rs806368 associated with PCOS. We observed a 3.6-fold increased risk of hyperandrogenemia (free androgen index – FAI > 7) in patients with GG genotype in the rs12720071 polymorphism and AA genotype in the polymorphism rs1049353 (OR = 2.7). Our study may indicate a role of the endocannabinoid system in the occurrence of a specific hyperandrogenemia phenotype of PCOS.

Chinese abstract

内源性大麻素系统被假定在肥胖、胰岛素抵抗、脂肪分布和代谢紊乱的病原学方面起重要作用。与腹型肥胖相关的胰岛素抵抗在多囊卵巢综合征（polycystic ovary syndrome，PCOS）雄激素增多症和其他临床特点的病因学上起主要作用。我们招募了174名16-38岁经鹿特丹诊断标准诊断的PCOS患者。对照组为125名18-45岁健康女性。我们对受试者采集病史，进行体格检查，收集人体测量参数和代谢指标。大麻素受体1（cannabinoid receptor 1，CNR1）基因多态性有六种。我们观察到PCOS患者在rs12720071位点多态性的GG基因型风险比对照组高出三倍（p=0.0344, OR=3.01）；类似的，PCOS患者在rs806368位点多态性的CC基因型风险比对照组高8倍（p=0.0176, OR=8.81）。我们也观察到rs12720071位点多态性的GG基因型和rs1049353位点多态性的AA基因型患者的高雄激素血症（free androgen index – FAI>7）风险增加了3.6倍（OR=2.7）。我们的研究可能表明内源性大麻素系统对PCOS一种特定的高雄激素血症表型的发生起作用。

• CNR1 polymorphism
• endocannabinoid system
• polycystic ovary syndrome

Declaration of interest

The authors have no conflicts of interest to disclose. This study was supported by research project no. 3188/B/P\P01/2010/39.