Sarray Sameh, Ezzidi Intissar, Ben Salem Assila, Ben Abdennebi Hassen, Mtiraoui Nabil
College of Medicine and Health Sciences, Arabian Gulf University, Manama, Bahrain.
Faculty of Sciences, University of Tunis EL Manar, Tunis, Tunisia.
Clin Endocrinol (Oxf). 2025 Aug;103(2):242-250. doi: 10.1111/cen.15269. Epub 2025 May 8.
Variants in the genes encoding anti-mullerian hormone (AMH) and its receptor 2 (AMHR2) have been identified as potential contributors to the development of polycystic ovary syndrome (PCOS). However, results from association studies examining their role in PCOS have been inconsistent. This study aims to investigate the potential association between AMH and AMHR2 gene variants and the risk of PCOS as well as their influence on serum AMH levels in a Tunisian cohort.
The case-control study recruited 327 PCOS women and 396 healthy controls. DNA was extracted and genotyped for three variants in the AMH gene namely, rs4807216, rs10407022 and rs8112524 as well as three variants in the AMHR2 gene, including rs2002555, rs11170553 and rs2272002, using the TaqMan SNP genotyping assay. Fasting serum AMH levels were quantified using ELISA.
Significant metabolic differences were observed in the PCOS cohort, including higher BMI, and elevated levels of AMH, glucose, triglycerides, and cholesterol, along with lower FSH levels. The investigation of genetic associations between AMH and AMHR2 gene variants and PCOS susceptibility revealed notable genotype-specific correlations with lipid profiles. Specifically, the AMH rs8112524 A/A and G/A genotypes were correlated to increased triglyceride levels, while the AMHR2 rs2002555 G/G genotype, as well as the rs11170553 T/T and C/T genotypes, were correlated with decreased HDL levels. However, no significant allelic, genotypic or haplotypic associations were identified, nor was any substantial impact on serum AMH levels observed. Additionally, interaction and epistasis analyses indicated that the AMH and AMHR2 variants had no significant predictive capabilities regarding PCOS susceptibility.
Although AMH and AMHR2 variants may not directly influence PCOS susceptibility, they could play a role in modulating lipid metabolism associated with the syndrome.
编码抗苗勒管激素（AMH）及其受体2（AMHR2）的基因变异已被确定为多囊卵巢综合征（PCOS）发病的潜在因素。然而，关于它们在PCOS中作用的关联研究结果并不一致。本研究旨在调查突尼斯人群中AMH和AMHR2基因变异与PCOS风险之间的潜在关联，以及它们对血清AMH水平的影响。
病例对照研究招募了327名PCOS女性和396名健康对照。使用TaqMan SNP基因分型检测法对AMH基因的三个变异位点rs4807216、rs10407022和rs8112524以及AMHR2基因的三个变异位点，包括rs2002555、rs11170553和rs2272002进行DNA提取和基因分型。使用酶联免疫吸附测定法（ELISA）对空腹血清AMH水平进行定量。
在PCOS队列中观察到显著的代谢差异，包括较高的体重指数（BMI），以及升高的AMH、血糖、甘油三酯和胆固醇水平，同时促卵泡生成素（FSH）水平较低。对AMH和AMHR2基因变异与PCOS易感性之间的遗传关联进行调查，发现与血脂谱存在显著的基因型特异性相关性。具体而言，AMH rs8112524 A/A和G/A基因型与甘油三酯水平升高相关，而AMHR2 rs2002555 G/G基因型以及rs11170553 T/T和C/T基因型与高密度脂蛋白（HDL）水平降低相关。然而，未发现显著的等位基因、基因型或单倍型关联，也未观察到对血清AMH水平有任何实质性影响。此外，相互作用和上位性分析表明，AMH和AMHR2变异对PCOS易感性没有显著的预测能力。
虽然AMH和AMHR2变异可能不会直接影响PCOS易感性，但它们可能在调节与该综合征相关的脂质代谢中发挥作用。
