Dedousi Dimitra, Mavrogianni Despoina, Papamentzelopoulou Myrto, Stavros Sofoklis, Raouasnte Rami, Loutradis Dimitris, Drakakis Peter
Molecular Biology Unit, Division of Human Reproduction, 1st Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Athens, Greece.
Horm Mol Biol Clin Investig. 2022 Jul 4;43(4):421-426. doi: 10.1515/hmbci-2021-0093. eCollection 2022 Dec 1.
The present case-control study investigates whether Arg72Pro variant (rs1042522) serves as a risk factor for recurrent pregnancy loss (RPL) in Greek women.
The study group consisted of 100 patients with at least two miscarriages of unexplained etiology, before the 24th week of gestation. The control group included 106 women with no pregnancy loss history. DNA was extracted and genotyped using specific primers for PCR amplification of the Arg72 and Pro72 alleles. Sanger sequencing was used for the discrimination between heterozygotes and homozygotes for Arg72Pro variant.
This is the first study demonstrating the statistically significant higher frequency of Arg72Pro variant in Greek RPL women compared to controls (38% vs. 6.6%; OR=8.6682, 95% CI: 3.6446-20.6160; p<0.0001). GC genotype (Arg/Pro) and CC genotype (Pro/Pro) were statistically more common in RPL patients than in controls (16% vs. 1.9%; p=0.0027, and 22 vs. 4.7%; p=0.0008, respectively). C allele frequency was statistically significant higher in RPL group than in controls (30.0 vs. 5.7%; p<0.0001). According to the inheritance mode analysis, the model that best fit the data was the dominant model (OR=8.67, 95% CI=3.64-20.62; p<0.0001).
The is the first study disclosing strong evidence that rs1042522 is significantly associated with a higher risk for recurrent pregnancy loss in Greek women following a dominant model, thus, serving as a genetic marker for identifying women at increased risk of recurrent miscarriages.
本病例对照研究旨在调查Arg72Pro变体（rs1042522）是否为希腊女性复发性流产（RPL）的危险因素。
研究组由100例在妊娠24周前有至少两次不明原因流产的患者组成。对照组包括106名无流产史的女性。提取DNA并使用特异性引物对Arg72和Pro72等位基因进行PCR扩增基因分型。采用桑格测序法区分Arg72Pro变体的杂合子和纯合子。
本研究首次表明，与对照组相比，希腊复发性流产女性中Arg72Pro变体的频率在统计学上显著更高（38%对6.6%；OR=8.6682，95%CI：3.6446 - 20.6160；p<0.0001）。GC基因型（Arg/Pro）和CC基因型（Pro/Pro）在复发性流产患者中在统计学上比对照组更常见（分别为16%对1.9%；p=0.0027，以及22%对4.7%；p=0.0008）。RPL组中C等位基因频率在统计学上显著高于对照组（30.0%对5.7%；p<0.0001）。根据遗传模式分析，最符合数据的模型是显性模型（OR=8.67，95%CI=3.64 - 20.62；p<0.0001）。
本研究首次揭示了有力证据，即rs1042522按照显性模式与希腊女性复发性流产的较高风险显著相关，因此，可作为识别复发性流产风险增加女性的遗传标志物。
