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

Abstract

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.

Association of human leukocyte antigen‐G and ‐F with recurrent miscarriage and implantation failure: A systematic review and meta‐analysis

“…Additionally, Najafi et al. found that the‐486A > C and −689A > G HLA‐G polymorphisms were significantly associated with RM 62 . The T1570C and C1594A HLA‐G polymorphisms were significantly associated with the risk of miscarriage after categorization based on the 14‐bp deletion 53 .…”

“…38,54 Additionally, Najafi et al found that the-486A > C and −689A > G HLA-G polymorphisms were significantly associated with RM. 62 The T1570C and C1594A HLA-G polymorphisms were significantly associated with the risk of miscarriage after categorization based on the 14-bp deletion. 53 In addition to the six SNPS summarized above, the remaining 23 SNPS, including 15 SNPs (+3422C/T, +3496A/G, +3509G/T, rs1611139, rs567747015, rs146339774, rs569057854, rs180827037, rs554784083, rs138249160, rs554076817, rs187320344, rs1233331, and rs541542414) in the HLA-G 3ʹUTR, two SNPS (−725C/G/T and rs1736936) in the promoter site, two SNPS (C8T and C20A) in intron 2, and three SNPS (+36G/A, Thr258Met, and Pro81Pro) in exons 1, 2, and 4, not found to be associated with the risk of RM.…”

“…Except for the eight SNPs that were meta-analyzed, we found 28 SNPs mentioned in nine articles. 32,38,40,41,43,53,54,[61][62][63] Of these, −725C/G and 1597ΔC (HLA-G*0105N) were reported twice in the context of women with RM, 32,38,54,63 while the rest were mentioned only once.…”

The Effects of HLA-G Gene Polymorphism and sHLA-G Level in Women with Threatened Abortion

“…The Human leukocyte antigen G promoter possesses various specificities, and the quantity of protein generated by HLA-G is altered by many polymorphisms in the HLA-G gene, including rs2735022 snp. Analysis of alleles, as well as genotypes frequency of rs2735022 amongst RPL with control participants, showed that allele risk (odds ratio=1.897) and genotype risk (odds ratio=1.932) was significant statistical (P=<0.05) between the two groups, and they exhibited a positive relationship with the recurrent pregnancy miscarriage [22]. Kim, S.K., et al investigated the influence of HLA-G gene promoter polymorphisms rs1736936 and rs2735022 on Rheumatoid arthritis in the Korean population.…”