HLA-G regulatory variants and haplotypes with susceptibility to recurrent pregnancy loss

HLA-G is a nonclassical Class I major histocompatibility complex (MHC) gene. This gene has a limited protein alteration that is produced by alternative splicing and can be important in the preservation of pregnancy. Recent findings suggest that alteration in HLA-G gene expression can lead to pregnancy failure, such as recurrent pregnancy loss (RPL). As the promoter SNPs of the gene may impact the HLA-G expression levels, the study of these SNPs is very important. In this study, for the promoter region of HLA-G gene in the case group (100 women with a history of two or more repeated miscarriages) and the control group (100 women with at least two successful pregnancies), PCR reaction was performed. Thereafter, PCR products were sequenced and the results were compared between the two groups. The results showed that -1573T>C and -1746C>A SNPs in the promoter of the HLA-G gene associated with RPL. The outcome of the haplotype analysis also showed that the association of two haplotypes, including H1 (ATCCAGGTACGCAA) and H2 (CTTCGAGAACGCAG) with RPL, is significant. The results showed that H1 is associated with a decreased and H2 is associated with an increased risk of RPL. These results indicate the importance of the HLA-G promoter SNPs in the pregnancy outcome. But to reach a more definite conclusion, subsequent studies on 3' UTR and other positions with polymorphism in the 5' UTR regions larger samples are necessary.