Almawi Wassim Y, Aimagambetova Gulzhanat, Tursunov Abay, Turesheva Akbayan, Marat Aizada, Ilmaliyeva Aktoty, Atageldiyeva Kuralay
Science Faculty of Tunisia, Université de Tunis El Manar, Tunis, Tunisia; Department of Biological Sciences, Brock University, St. Catharines, ON, Canada.
Department of Surgery, School of Medicine, Nazarbayev University, Astana, Kazakhstan; Clinical Academic Department of Women's Health, CF "University Medical Center", Astana 010000, Kazakhstan.
J Reprod Immunol. 2025 Jun;169:104524. doi: 10.1016/j.jri.2025.104524. Epub 2025 Mar 24.
Emerging evidence implicates immune dysfunction in maintaining maternal-fetal tolerance, particularly the programmed death-ligand 1 (PD-L1) pathway. The association between PD-L1 gene variants and recurrent pregnancy loss (RPL) in women from Central and West Kazakhstan was investigated, and correlations between PD-L1 genotypes and demographic or clinical features were explored. This case-control study included 197 women with RPL and 198 controls of ethnically Kazakh women. Genotyping of rs2297136, rs2297137, rs4143815, rs822336, and rs822337 PD-L1 variants was performed by real-time PCR. Demographic and clinical characteristics did not differ significantly between RPL cases and controls from Central and West Kazakhstan. Significant associations were found in the West Kazakhstan cohort for rs822336 (p = 0.02) and rs822337 (p = 0.004). The G/C genotype of rs822336 (OR = 2.33, 95 % CI = 1.04-5.26) and rs822337 (OR = 308, 95 % CI = 1.34-7.04) was associated with an increased risk of RPL in West Kazakhstan cohort. Haplotype analysis revealed a significant association of the GTGAG haplotype with RPL in West Kazakhstan (p = 0.018) but not in Central Kazakhstan subjects. Correlation analysis showed that rs822336 was positively correlated with age and BMI (p < 0.05) in Central Kazakhstan, while rs822337 was negatively correlated with live births in West Kazakhstan (p < 0.05). The findings underscore population-specific genetic influences on RPL risk, with notable significant associations between RPL and PD-L1 SNPs and GTGAG haplotype in the West Kazakhstan cohort but not in the Central Kazakhstan cohort. This highlights the contribution of genetic factors to RPL pathogenesis in different populations.
新出现的证据表明免疫功能障碍在维持母胎耐受中起作用，尤其是程序性死亡配体1（PD-L1）途径。本研究调查了哈萨克斯坦中西部女性中PD-L1基因变异与复发性流产（RPL）之间的关联，并探讨了PD-L1基因型与人口统计学或临床特征之间的相关性。这项病例对照研究纳入了197例RPL女性和198例哈萨克族对照女性。通过实时PCR对PD-L1基因变异rs2297136、rs2297137、rs4143815、rs822336和rs822337进行基因分型。哈萨克斯坦中西部的RPL病例和对照之间的人口统计学和临床特征没有显著差异。在哈萨克斯坦西部队列中，rs822336（p = 0.02）和rs822337（p = 0.004）存在显著关联。rs822336的G/C基因型（OR = 2.33，95%CI = 1.04 - 5.26）和rs822337的G/C基因型（OR = 3.08，95%CI = 1.34 - 7.04）与哈萨克斯坦西部队列中RPL风险增加相关。单倍型分析显示，GTGAG单倍型与哈萨克斯坦西部的RPL存在显著关联（p = 0.018），但在哈萨克斯坦中部人群中无此关联。相关性分析表明，在哈萨克斯坦中部，rs822336与年龄和BMI呈正相关（p < 0.05），而在哈萨克斯坦西部，rs822337与活产呈负相关（p < 0.05）。这些发现强调了特定人群的遗传因素对RPL风险的影响，在哈萨克斯坦西部队列中，RPL与PD-L1单核苷酸多态性和GTGAG单倍型之间存在显著关联，而在哈萨克斯坦中部队列中则没有。这突出了遗传因素在不同人群RPL发病机制中的作用。
