Amin M, Perrelli M, Wu R, Gragnoli C
INSERM, US14-Orphanet, Paris, France.
Eur Rev Med Pharmacol Sci. 2023 Feb;27(3):942-948. doi: 10.26355/eurrev_202302_31187.
Polycystic ovarian syndrome (PCOS) is a complex heterogeneous disorder characterized by hyperandrogenism, irregular menses, and subfertility and often accompanied by other related comorbid disorders such as insulin resistance, obesity, and type 2 diabetes. Several genetic risk factors predispose to PCOS, but most are still unknown. Up to 30% of women with PCOS may have hyperaldosteronism. Blood pressure and the ratio of blood levels of aldosterone to renin are higher in women with PCOS compared to healthy controls, even if still in the normal range; and the aldosterone antagonist spironolactone has been used as therapy for PCOS, mainly due to its antiandrogenic activity. Thus, we aimed to investigate the potential pathogenetic role of the mineralocorticoid receptor gene (NR3C2) as the encoded NR3C2 product binds aldosterone and plays a role in folliculogenesis, fat metabolism, and insulin resistance.
Within 212 Italian families with T2D and phenotyped for PCOS, we analyzed 91 single nucleotide polymorphisms in the NR3C2 gene. We tested the NR3C2 variants for linkage and linkage disequilibrium to the PCOS phenotype by using parametric analysis.
We found 18 novel risk variants significantly linked to and/or associated with the risk of PCOS.
We are the first to report NR3C2 as a risk gene in PCOS. However, our findings need to be replicated in other ethnic groups in order to reach more solid conclusions.
多囊卵巢综合征（PCOS）是一种复杂的异质性疾病，其特征为高雄激素血症、月经不规律和生育力低下，常伴有其他相关合并症，如胰岛素抵抗、肥胖和2型糖尿病。有几种遗传风险因素易导致PCOS，但大多数仍不明确。高达30%的PCOS女性可能患有醛固酮增多症。与健康对照相比，PCOS女性的血压以及醛固酮与肾素的血水平比值更高，即便仍在正常范围内；醛固酮拮抗剂螺内酯已被用作PCOS的治疗药物，主要因其具有抗雄激素活性。因此，我们旨在研究盐皮质激素受体基因（NR3C2）的潜在致病作用，因为其编码产物NR3C2可结合醛固酮，并在卵泡发生、脂肪代谢和胰岛素抵抗中发挥作用。
在212个患有2型糖尿病且已对PCOS进行表型分析的意大利家庭中，我们分析了NR3C2基因中的91个单核苷酸多态性。我们通过参数分析测试了NR3C2变异体与PCOS表型的连锁和连锁不平衡情况。
我们发现18个新的风险变异体与PCOS风险显著连锁和/或相关。
我们首次报道NR3C2是PCOS的一个风险基因。然而，我们的研究结果需要在其他种族群体中进行重复验证，以便得出更可靠的结论。
