Mir Rashid, Saeedi Nizar H, Jalal Mohammed M, Altayar Malik A, Barnawi Jameel, Hamadi Abdullah, Tayeb Faris J, Alshammari Sanad E, Mtiraoui Nabil, M Ali Mohammed Eltigani, Abuduhier Faisel M, Ullah Mohammad Fahad
Faculty of Applied Medical Science, University of Tabuk, Tabuk 71491, Saudi Arabia.
Department of Medical Laboratory Technology, Faculty of Applied Medical Science, University of Tabuk, Tabuk 71491, Saudi Arabia.
J Pers Med. 2022 Apr 6;12(4):586. doi: 10.3390/jpm12040586.
Polycystic ovary syndrome (PCOS) is a disorder with a symptomatic manifestation of an array of metabolic and endocrine impairments. PCOS has a relatively high prevalence rate among young women of reproductive age and is a risk factor for some severe metabolic diseases such as T2DM, insulin insensitivity, and obesity, while the most dominant endocrine malfunction is an excess of testosterone showing hyperandrogenism and hirsutism. MicroRNAs have been implicated as mediators of metabolic diseases including obesity and insulin resistance, as these can regulate multiple cellular pathways such as insulin signaling and adipogenesis. Genome-wide association studies during the last few years have also linked the Krüpple-like family of transcription factors such as KLF14, which contribute in mechanisms of mammalian gene regulation, with certain altered metabolic traits and risk of atherosclerosis and type-2 DM. This study has characterized the biochemical and endocrine parameters in PCOS patients with a comprehensive serum profiling in comparison to healthy controls and further examined the influence of allelic variations for miRNAs 27a (rs895819 A > G), 196a2 (rs11614913 C > T), 423 (rs6505162C > A), and transcription factor KLF14 (rs972283 A > G) gene polymorphism on the risk and susceptibility to PCOS. The experimental protocol included amplification refractory mutation-specific (ARMS)-PCR to detect and determine the presence of these polymorphic variants in the study subjects. The results in this case−control study showed that most of the serum biomarkers, both biochemical and endocrine, that were analyzed in the study demonstrated statistically significant alterations in PCOS patients, including lipids (LDL, HDL, cholesterol), T2DM markers (fasting glucose, free insulin, HOMA-IR), and hormones (FSH, LH, testosterone, and progesterone). The distribution of Krüppel-like factor 14 rs972283 G > A, miR-27a rs895819 A > G, and miR-196a-2 rs11614913 C > T genotypes analyzed within PCOS patients and healthy controls in the considered population was significant (p < 0.05), except for miR-423 rs6505162 C > A genotypes (p > 0.05). The study found that in the codominant model, KLF14-AA was strongly associated with greater PCOS susceptibility (OR 2.35, 95% CI = 1.128 to 4.893, p < 0.022), miR-27a-GA was linked to an enhanced PCOS susceptibility (OR 2.06, 95% CI = 1.165 to 3.650, p < 0.012), and miR-196a-CT was associated with higher PCOS susceptibility (OR 2.06, 95% CI = 1.191 to 3.58, p < 0.009). Moreover, allele A of KLF-14 and allele T of miR-196a2 were strongly associated with PCOS susceptibility in the considered population.
多囊卵巢综合征（PCOS）是一种具有一系列代谢和内分泌障碍症状表现的疾病。PCOS在育龄年轻女性中患病率相对较高，是一些严重代谢疾病如2型糖尿病（T2DM）、胰岛素不敏感和肥胖的危险因素，而最主要的内分泌功能障碍是睾酮过多，表现为高雄激素血症和多毛症。微小RNA（MicroRNAs）被认为是包括肥胖和胰岛素抵抗在内的代谢疾病的介质，因为它们可以调节多种细胞途径，如胰岛素信号传导和脂肪生成。过去几年的全基因组关联研究还将Krüpple样转录因子家族（如KLF14）与某些代谢特征改变、动脉粥样硬化风险和2型糖尿病联系起来，KLF14参与哺乳动物基因调控机制。本研究通过全面的血清分析对PCOS患者的生化和内分泌参数进行了特征描述，并与健康对照进行比较，进一步研究了微小RNA 27a（rs895819 A > G）、196a2（rs11614913 C > T）、423（rs6505162C > A）以及转录因子KLF14（rs972283 A > G）基因多态性对PCOS风险和易感性的影响。实验方案包括采用扩增阻滞突变系统聚合酶链反应（ARMS-PCR）来检测和确定研究对象中这些多态性变体的存在。该病例对照研究结果显示，研究中分析的大多数血清生物标志物，包括生化和内分泌指标，在PCOS患者中均表现出统计学上的显著改变，包括脂质（低密度脂蛋白、高密度脂蛋白、胆固醇）、T2DM标志物（空腹血糖、游离胰岛素、胰岛素抵抗稳态模型评估）和激素（促卵泡生成素、促黄体生成素、睾酮和孕酮）。在该研究人群中，PCOS患者和健康对照中分析的Krüppel样因子14 rs化、196a-2 rs11614913 C > T基因型的分布具有显著性差异（p < 0.05），但miR-423 rs6505162 C > A基因型除外（p > 0.05）。研究发现，在共显性模型中，KLF14-AA与更高的PCOS易感性密切相关（比值比2.35，95%置信区间 = 1.128至4.893，p < 0.022），miR-27a-GA与PCOS易感性增强有关（比值比2.06，95%置信区间 = 1.165至3.650，p < 0.012），miR-196a-CT与更高的PCOS易感性相关（比值比2.06，95%置信区间 = 1.191至3.58，p < 0.009）。此外，在该研究人群中，KLF-14的A等位基因和miR-196a2的T等位基因与PCOS易感性密切相关。
