Association between HLA-E gene polymorphism and unexplained recurrent spontaneous abortion (RSA) in Iranian women

Abstract

Background:Human leukocyte antigen-E (HLA-E)is a non-classical major histocompatibility complex (MHC) class I antigens which expressed on extra villous cytotrophoblast, which interacts with NKG2A, is an inhibitory receptor on natural killer (NK) cells and leading to down regulation of immune response in the maternal-fetal interface and provides maternal immune tolerance of the fetus.Objective:This study was designated to investigate the gene frequencies of E0101 and E0103 in HLA-E gene in Iranian women with recurrent spontaneous abortion (RSA). Materials and Methods:Amplification Refractory Mutation System (ARMS-PCR) technique was carried out to detect polymorphism in exon 3 of the HLA-E gene in women with RSA and controls (n=200). Differences between groups were analyzed by SPSS19 software using 2 test.Results:There was no significant difference in the allele frequencies of the HLA-E polymorphism between RSA and fertile controls but HLA-E 0101/0103 heterozygous genotype was found to be significantly higher in RSA group (p=0.006, OR=1.73), so this genotype might confer susceptibility to RSA.Conclusion: Our results suggest that HLA-E 0101/0103 heterozygous genotype leads to increase of RSA risk. It seems that by genotyping of HLA-E polymorphism, we can predict the risk of RSA in infertile women.

Expression of Human Leukocyte Antigen-E and Natural Killer Cells in Intra Uterine Fetal Death

“…The mean expression of NK cells in the trophoblast on IUFD was higher compared to normal pregnancy. The results of this study were in line with the research conducted by Fotoohi in 2016 that obtained lower HLA-E in recurrent spontaneous abortion including IUFD than normal pregnancy because HLA-E is an antigen that interact with NKG2A which is a receptor inhibitor of NK cells that help the fetus to face the response of maternal immunity, so when HLA-E deficiency occurs, the fetus is more vulnerable to NK cells attack that will cause IUFD (Fotoohi et al 2016).…”

“…HLA-E can protect trophoblast from maternal-fetal immune intolerance and allow the trophoblast cells to invade the uterus. HLA-E plays an important role in immune tolerance during pregnancy (Fotoohi et al 2016).…”

European Patent in Immunoncology: From Immunological Principles of Implantation to Cancer Treatment

“…In addition to HLA-G polymorphisms, an association between HLA-E polymorphisms and RSAs has been observed. The HLA-E 0101 allele, compared with the HLA-E 0103 allele, was significantly higher in women suffering from RSAs [127].…”

Genetics of recurrent pregnancy loss among Iranian population

“…It has been observed that there was higher frequency of HLA‐E 0101 polymorphism among a sample of Iranian RSA cases compared with controls, whereas HLA‐E 0103 was more frequent among controls. Moreover, the HLA‐E0101/0103 heterozygous genotype was correlated with fetus maintenance among Iranians (Fotoohi, Ghasemi, Mirghanizadeh, Vakili, & Samadi, ).…”