Robeva Ralitsa, Andonova Silvia, Todorov Tihomir, Feyzullova Aylin, Elenkova Atanaska, Kirilov Georgi, Savov Alexey, Zacharieva Sabina, Todorova Albena
Department of Endocrinology, Medical Faculty, Medical University-Sofia, USHATE "Acad. Iv. Penchev", 1000 Sofia, Bulgaria.
National Genetic Laboratory, Medical Faculty, Medical University-Sofia, University Hospital of Obstetrics and Gynecology "Maichin Dom", 1000 Sofia, Bulgaria.
Biomedicines. 2024 Jul 9;12(7):1528. doi: 10.3390/biomedicines12071528.
Pathogenic variants in the gene are related to the classic and non-classic forms of congenital adrenal hyperplasia (CAH). However, the role of CAH carrier status in the clinical presentation of polycystic ovarian syndrome (PCOS) is still unclear. Moreover, the possible associations of different gene polymorphisms with metabolic and reproductive abnormalities in PCOS have not been investigated. Therefore, the present study aims to examine the prevalence of the most common pathogenic variant IVS2-13A/C>G (c.293-13A/C>G) in Eastern European women with PCOS and to evaluate the associations between common intron 2 genetic polymorphisms and the clinical symptoms of the patients.
Sixty consecutively recruited women with PCOS were genotyped for the intron 2 IVS2-13A/C>G genetic variant. Additionally, intron 2 polymorphic variants rs6453 (c.293-44G>T), rs6451 (c.293-67C>A/G), rs369651496 (c.293-104del), and rs6474 (c.308G>A/p.R103L) were tested and described. The clinical and hormonal characteristics were compared in women with PCOS and with polymorphic and wild-type genotypes.
The heterozygous pathogenic variant IVS2-13A/C>G was found in one of the investigated PCOS patients (1.67%) with a non-hyperandrogenic type of PCOS. The presence of the rs6453 (c.293-44G>T) T-allele was associated with increased levels of DHEAS (15.18 vs. 9.14 µmol/L, = 0.003) compared to the wild-type genotype in the investigated group. The rs6451 (c.293-67C>A/G) minor alleles were associated with an earlier age of menarche in the patients (12.0 vs. 13.0 years, = 0.007). The polymorphic rs369651496 minor 6G allele was related to a better lipid profile in the women with PCOS, while the rs6474 variant modulated the blood pressure of the patients.
The presence of genetic minor alleles of rs6467 (IVS2-13A/C, c.293-13A/C), rs6453 (c.293-44G>T), rs6451 (c.293-67C>A/G), rs369651496 (c.293-104del), and rs6474 (c.308G>A/p.R103L) might modulate the adrenal androgens, age of menarche, and metabolic features in women with PCOS. Further studies on 21-hydroxylase genetic variants (pathogenic and polymorphisms) in different ethnic groups might help reveal the influence of adrenal steroidogenesis on PCOS development, clinical manifestations, and lifelong cardiovascular risks.
该基因的致病变异与先天性肾上腺皮质增生症（CAH）的经典型和非经典型有关。然而，CAH携带者状态在多囊卵巢综合征（PCOS）临床表现中的作用仍不清楚。此外，不同基因多态性与PCOS代谢和生殖异常之间可能的关联尚未得到研究。因此，本研究旨在检测东欧PCOS女性中最常见的致病变体IVS2-13A/C>G（c.293-13A/C>G）的患病率，并评估常见内含子2基因多态性与患者临床症状之间的关联。
对连续招募的60例PCOS女性进行内含子2 IVS2-13A/C>G基因变体的基因分型。此外，还检测并描述了内含子2多态性变体rs6453（c.293-44G>T）、rs6451（c.293-67C>A/G）、rs369651496（c.293-104del）和rs6474（c.308G>A/p.R103L）。比较了PCOS患者以及具有多态性和野生型基因型患者的临床和激素特征。
在一名接受调查的非高雄激素型PCOS患者中发现了杂合致病变体IVS2-13A/C>G（1.67%）。与研究组中的野生型基因型相比，rs6453（c.293-44G>T）T等位基因的存在与硫酸脱氢表雄酮水平升高有关（15.18对9.14μmol/L，P=0.003）。rs6451（c.293-67C>A/G）次要等位基因与患者初潮年龄较早有关（12.0对13.0岁，P=0.007）。多态性rs369651496次要6G等位基因与PCOS女性更好的血脂谱有关，而rs6474变体调节了患者的血压。
rs6467（IVS2-13A/C，c.293-13A/C）、rs6453（c.
