Haplotype Effect of Two Human Leukocyte Antigen-G Polymorphisms of rs1736933 and rs2735022 on the Recurrent Pregnancy Loss

Background: Recurrent Pregnancy Loss (RPL) is a multifactorial disease that affects 1-3% of couples. Since Human Leukocyte Antigen-G (HLA-G) gene is involved in fetal maternal immune tolerance, mutations in the HLA-G gene can affect the success rate of pregnancy. Objective: The present study aims to investigate the haplotype effect of rs1736933 and rs2735022 polymorphisms found in the HLA-G gene on the RPL. Methods In this case-control study, participants were 100 women with RPL and 80 women with normal fertility in northwestern Iran. The HLA-G gene promoter was amplified by Polymerase Chain Reaction (PCR) method and sequenced. The genotype and allele frequencies of the two polymorphisms were compared between the two groups by using t-test in SPSS software version 22. Haplotype analysis was performed using PHASE 2.1 and Haploview 4.2 applications Findings: C allele and CC genotype in rs2735022 polymorphism and the G allele and GG genotype in rs1736933 polymorphism showed a significant association with the RPL (P<0.05). Frequency of haplotypes AA, AC, GA, GC were 0.72, 0.23, 0.01, 0.03 in patients and 0.39, 0.01, 0.02, 0.59 in the control group (P<0.05). The linkage disequilibrium score was 94. Conclusion: Analysis of GC haplotype in rs2735022 and rs1736933 polymorphisms of the HLA-G gene can be helpful in genetic studies of women with RPL.