A study on genetic polymorphisms associated with unexplained recurrent pregnancy loss in south indian population

Abstract

Recurrent pregnancy loss is a multifactorial, heterogeneous condition, with obscure etiology in about half of the cases. Immunological as well as genetic factors are reported to contribute significantly towards the maintenance of pregnancy. From an immunological point of view, the fetus is a foreign graft and immunomodulation is an initiating event for the acceptance of this semi-allogenic fetus by maternal immune cells. Following appropriate immunomodulation, it is essential that the vascular remodeling, xenobiotic metabolism and DNA repair pathways function normally and synergistically to enable the successful survival of the fetus in the maternal environment. Failure to control maternal immune response against the fetal tissues or alterations in any of the other pathways is believed to lead to adverse pregnancy outcome such as RPL. The increased incidence rates and unknown etiology of RPL stressed the need to identify genetic markers for predisposition. Hence the present study aimed at identifying the role of genetic polymorphism in the immunomodulatory genes (HLA G, KIR) as well as genes regulating the vascular remodelling (VEGF, ACE and MTHFR), xenobiotic metabolism (CYP1A1, GSTM1, GSTT1 and GSTP1) and DNA repair (XRCC1 and XPD). The study comprised of hundred and four couples with unexplained RPL. The controls for the study were eighty couples and an additional of forty women with at least two children and no history of RPL. High molecular weight genomic DNA was isolated from the peripheral blood samples collected from the study subjects and the polymorphisms were analyzed by PCR based methods. Immunomodulatory gene analysis revealed a significantly increased frequency of HLA G*0105N and HLA G I/D genotype in RPL women compared to the controls. In the partners of RPL and control women there was no significant difference in the HLA G alleles. However, sharing of G*0104 allele between the couples contributed significantly to RPL.