Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Rocky Mountain Mental Illness Research Education and Clinical Center (MIRECC), Consortium for Research and Education (MVM-CoRE), Denver, CO, 80246, USA.
J Ovarian Res. 2024 Jan 13;17(1):17. doi: 10.1186/s13048-024-01343-1.
Polycystic ovarian syndrome (PCOS) is a genetically complex disorder that involves the interplay of multiple genes and environmental factors. It is characterized by anovulation and irregular menses and is associated with type 2 diabetes. Neuroendocrine pathways and ovarian and adrenal dysfunctions are possibly implicated in the disorder pathogenesis. The melatonin system plays a role in PCOS. Melatonin receptors are expressed on the surface of ovarian granulosa cells, and variations in the melatonin receptor genes have been associated with increased risk of PCOS in both familial and sporadic cases. We have recently reported the association of variants in MTNR1A and MTNR1B genes with familial type 2 diabetes. In this study, we aimed to investigate whether MTNR1A and MTNR1B contribute to PCOS risk in peninsular families. In 212 Italian families phenotyped for PCOS, we amplified by microarray 14 variants in the MTNR1A gene and 6 variants in the MTNR1B gene and tested them for linkage and linkage disequilibrium with PCOS. We detected 4 variants in the MTNR1A gene and 2 variants in the MTNR1B gene significantly linked and/or in linkage disequilibrium with the risk of PCOS (P < 0.05). All variants are novel and have not been reported before with PCOS or any of its related phenotypes, except for 3 variants previously reported by us to confer risk for type 2 diabetes and 1 variant for type 2 diabetes-depression comorbidity. These findings implicate novel melatonin receptor genes' variants in the risk of PCOS with potential functional roles.
多囊卵巢综合征（PCOS）是一种遗传复杂的疾病，涉及多个基因和环境因素的相互作用。它的特征是无排卵和不规则的月经，并且与 2 型糖尿病有关。神经内分泌途径以及卵巢和肾上腺功能障碍可能与该疾病的发病机制有关。褪黑素系统在 PCOS 中起作用。褪黑素受体表达在卵巢颗粒细胞的表面，褪黑素受体基因的变异与家族性和散发性 PCOS 的风险增加有关。我们最近报道了 MTNR1A 和 MTNR1B 基因变异与家族性 2 型糖尿病的关联。在这项研究中，我们旨在研究 MTNR1A 和 MTNR1B 是否会导致半岛家族的 PCOS 风险增加。在对 212 个意大利 PCOS 表型家族进行微阵列扩增后，我们检测了 MTNR1A 基因中的 14 个变体和 MTNR1B 基因中的 6 个变体，以检测它们与 PCOS 的连锁和连锁不平衡。我们检测到 MTNR1A 基因中的 4 个变体和 MTNR1B 基因中的 2 个变体与 PCOS 的风险显著连锁和/或连锁不平衡（P<0.05）。所有变体都是新的，以前没有报道过与 PCOS 或其任何相关表型有关，除了我们以前报道的 3 个与 2 型糖尿病有关的变体和 1 个与 2 型糖尿病-抑郁症共病有关的变体。这些发现表明新的褪黑素受体基因变异与 PCOS 的风险有关，并具有潜在的功能作用。
