Ramanathan Balaji, Murugan Jeyasudha, Velayutham Kumaravel
Department of Molecular Genetics, Alpha Health Foundation, Madurai, Tamil Nadu, India.
Indian J Endocrinol Metab. 2021 Nov-Dec;25(6):551-558. doi: 10.4103/ijem.ijem_340_21. Epub 2022 Feb 17.
Polycystic ovarian syndrome (PCOS) is typically characterized by a spectrum of manifestations that include menstrual irregularities, anovulation, cysts, hyperandrogenic features like hirsutism, acne, alopecia, and various metabolic complications. The pathology of PCOS is complex and several mechanisms have been potentially involved in the genetic abnormalities/dysfunctions. Hence, the present study aims to examine the prevalence and association of polymorphisms in candidate genes (thyroid adenoma-associated gene [THADA], luteinizing hormone and human chorionic gonadotropin receptor [LHCGR], DENN domain containing 1A [DENND1A], follicle-stimulating hormone receptor [FSHR], Connexin37 [CX37], angiotensin-converting enzyme [ACE], insulin receptor [INSR] and calpain 10 [CAPN10]) in PCOS patients of the South Indian regional population.
The study group included 20 PCOS cases and 10 controls, whose deoxyribonucleic acid (DNA) were genotyped by the polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (RFLP), and PCR product sequencing to determine the prevalence of the DENND1A (rs10818854), LHCGR (rs13405728), FSHR (rs2349415), THADA (rs13429458), CX37 (rs1764391), ACE (rs1799752), INSR (rs1799817), and CAPN10 (rs2975760) polymorphisms. Clinical examinations including anthropometric measurements, biochemical investigations relevant to glucose metabolism, and hormones were measured.
A significant difference was observed in the DENND1A (rs10818854) polymorphism between the control and PCOS patients ( = 0.001). The variants of LHCGR, FSHR, THADA, CX37, ACE, INSR, and CAPN10 were not statistically significant with PCOS. The body mass index (BMI) ( = 0.01), triglycerides ( = 0.01), and dehydroepiandrosterone sulfate (DHEAS) ( = 0.05) were significantly different between the PCOS patients and controls. Significant results were observed in rs1799817 single nucleotide polymorphisms (SNP) of INSR with elevated levels of triglycerides and rs10818854 of DENND1A, rs13429458 of THADA, rs2349415 of FSHR with the high levels of DHEAS.
In the study population, the presence of rs10818854 of DENND1A polymorphism may be associated with the risk of PCOS and high levels of DHEAS.
多囊卵巢综合征（PCOS）通常具有一系列表现，包括月经不规律、无排卵、囊肿、多毛症、痤疮、脱发等高雄激素特征以及各种代谢并发症。PCOS的病理机制复杂，多种机制可能与基因异常/功能障碍有关。因此，本研究旨在调查南印度地区人群PCOS患者中候选基因（甲状腺腺瘤相关基因[THADA]、促黄体生成素和人绒毛膜促性腺激素受体[LHCGR]、含DENN结构域蛋白1A[DENND1A]、促卵泡激素受体[FSHR]、连接蛋白37[CX37]、血管紧张素转换酶[ACE]、胰岛素受体[INSR]和钙蛋白酶10[CAPN10]）多态性的患病率及其相关性。
研究组包括20例PCOS患者和10例对照，通过聚合酶链反应（PCR）、PCR-限制性片段长度多态性（RFLP）和PCR产物测序对其脱氧核糖核酸（DNA）进行基因分型，以确定DENND1A（rs10818854）、LHCGR（rs13405728）、FSHR（rs2349415）、THADA（rs13429458）、CX37（rs1764391）、ACE（rs1799752）、INSR（rs1799817）和CAPN10（rs2975760）多态性的患病率。进行了包括人体测量、与糖代谢相关的生化检查以及激素检测在内的临床检查。
在对照组和PCOS患者之间，DENND1A（rs10818854）多态性存在显著差异（P = 0.001）。LHCGR、FSHR、THADA、CX37、ACE、INSR和CAPN10的变体与PCOS无统计学显著差异。PCOS患者和对照组之间的体重指数（BMI）（P = 0.01）、甘油三酯（P = 0.01）和硫酸脱氢表雄酮（DHEAS）（P = 0.05）有显著差异。观察到INSR的rs1799817单核苷酸多态性（SNP）与甘油三酯水平升高以及DENND1A的rs10818854、THADA的rs13429458、FSHR的rs2349415与高水平的DHEAS之间存在显著结果。
在研究人群中，DENND1A基因rs10818854多态性的存在可能与PCOS风险和高水平的DHEAS有关。
