Allelic and genotypic frequencies of HLA-G upstream polymorphism rs۲۷۳۵۰۲۲ and association with recurrent spontaneous abortion in the northwest of Iran women population

Background and Aim: Abortion, as defined by the World Health Organization, means termination of pregnancy before the twentieth week of pregnancy or the birth of a fetus weighing less than ۵۰۰ grams. Recurrent abortion is a multifactorial disease that effects ۱ to ۳ percent of couples. So far, the effect of several genetic factors including chromosomal abnormalities, anatomy, hormonal and immunological abnormalities have been investigated. However, half of its causes remain unclear in most patients. Among the most common genes in the field of recurrent miscarriage, genes related to maternal metabolism and blood embolism, inflammation and immune tolerance may be mentioned. HLA-G gene in fetal tissue, genetic susceptibility and its role in the defense of maternal and fetal immunity are likely to influence the success of pregnancy in gene mutation and alteration in HLA-G. Therefore, the present study was performed to investigate the association of the HLA-G upstream rs۲۷۳۵۰۲۲ polymorphism with recurrent spontaneous abortion in northwestern of Iran women population Methods: This case-control study was performed on ۱۰۰ women with recurrent spontaneous abortion and ۸۰ individuals with normal fertility referred to Tabriz Maternal Clinic. After preparation of blood samples and DNA extraction, HLA-G gene promoter fragment was amplified in both patient and control groups by polymerase chain reaction (PCR) and analyzed by agarose gel electrophoresis. After confirmation of PCR reaction, case and control samples were sent for sequencing. After sequencing, genotypes were determined by Chromas software. After determining the allelic and genotypic frequencies for patient and control groups, the frequencies were compared by t-test and SPSS software.Results: For Polymorphism rs۲۷۳۵۰۲۲ in this study, the genotypes of patient group AA, GA, GG and their frequency were ۷ (۷), ۳۶ (۳۶), ۵۷ (۵۷) and control group's frequency with the same genotypes respectively, was ۱۵ (۱۸.۷۵), ۳۳ (۴۱.۲۵), ۳۲ (۴۰). The calculated P-values respectively, was ۰.۰۱۳, ۰.۲۶۹, ۰.۰۱۲ and GG homozygous genotype showed positive association with recurrent abortion. The allelic frequency of rs ۲۷۳۵۰۲۲ A, G in patient group respectively, was ۵۰ (۲۵) and ۱۵۰ (۷۵). but in control group was ۶۳ (۳۹.۳۷), ۹۷ (۶۰.۶۳) and G allele had a positive association with recurrent abortion. Since P <۰.۰۵ was considered statistically significant in this study, a significant difference was observed between the two groups comparison.Conclusion: In this study, polymorphisms of rs۲۷۳۵۰۲۲ upstream of HLA-G gene were associated with recurrent abortion with unknown cause in Northwestern Iranian population.

کلیدواژه ها:

Recurrent abortion ، Polymorphism ، Promoter ، HLA-G