PD-L1 gene variants as predictors of recurrent pregnancy loss: A case-control study among Kazakh women in Central and West Kazakhstan

Almawi W.Y. Aimagambetova G. Tursunov A. Turesheva A. Marat A. Ilmaliyeva A. Atageldiyeva K.
June 2025 Elsevier Ireland Ltd

Journal of Reproductive Immunology
2025 #169

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.

Genetic association , Kazakhstan , PD-L1 , Recurrent pregnancy loss , Single nucleotide polymorphism

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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 Womens Health, CF “University Medical Center”, Astana, 010000, Kazakhstan
School of Medicine, Nazarbayev University, Astana, Kazakhstan
Department of Normal Physiology, West-Kazakhstan Marat Ospanov Medical University, Aktobe, 030000, Kazakhstan
Department of Obstetrics and Gynecology #1, NJSC “Astana Medical University”, Astana, Kazakhstan
Department of Medicine #3, NJSC “Astana Medical University”, Astana, 010000, Kazakhstan
Department of Medicine, School of Medicine, Nazarbayev University, Astana, Kazakhstan
Clinical Academic Department of Internal Medicine, CF “University Medical Center”, Astana, 010000, Kazakhstan

Science Faculty of Tunisia
Department of Biological Sciences
Department of Surgery
Clinical Academic Department of Womens Health
School of Medicine
Department of Normal Physiology
Department of Obstetrics and Gynecology #1
Department of Medicine #3
Department of Medicine
Clinical Academic Department of Internal Medicine

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