The role of HLA-G gene polymorphism in the formation of pathology in maternal-fetal interface

The relation between polymorphic variants of the HLA-G gene and various pregnancy complications (failure after in vitro fertilization, preeclampsia, spontaneous abortions) is discussed. However, research results vary among women in different populations. It remains unknown whether maternal HLA-G alleles can control congenital malformations (CMs) in the fetus. We studied the role of HLA-G gene polymorphism in the formation of pathology in in maternal-fetal interface using the example of recurrent miscarriage (RM) and CMs in the fetus. We studied 461 women with reproductive pathology and 407 healthy and fertile women having 1-2 children and with no history of pathological pregnancy (control group). The RM group included 151 women with miscarriages before 20 weeks of pregnancy (min = 2; max = 6). The CM group consisted of 310 women with congenital malformations of the fetus. The diagnosis of CM type was carried out according to the International Classification of Diseases, Injuries and Conditions Affecting the Health, Tenth Revision (Q00-Q99). All women provided written informed consent to participate in the study. The rs41551813, rs12722477 and rs41557518 loci of the HLA-G gene were typed by asymmetric real-time PCR. HLA-G 14 bp Ins/Del polymorphism (rs66554220) was determined using electrophoretic separation of amplification products. Polymorphic loci rs41557518 and rs66554220 of HLA-G were linked disequilibrium (D’ = 0.808 (r = 0.017), χ² = 14.67, d(f) = 3, p = 0.002). Found only highly significant the association of the 110Ile HLA-G allele with the risk of RM in women after statistical correction (OR = 3.03 (1.97-4.64), p_cor < 0.0006). Found no statistically significant associations of polymorphic loci rs41551813, rs41557518 and rs66554220 of the HLA-G gene with RM in women. Found no associations of maternal HLA-G polymorphic loci with the risk of CMs in the fetus. It seems the role of individual the HLA-G polymorphic loci in the formation of CMs in the fetus may be minimal. The association of the 110Ile allele (HLA-G*01:04) with RM in women is likely due to its recessive effects on local inflammation.

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