Association of Alu I polymorphism in estrogen receptor beta gene with adverse pregnancy outcome in HEV infection

Abstract

Hepatitis E has both a high incidence and severe course in pregnant women in some geographic regions of HEV (Hepatitis E virus) endemic countries. Intrauterine fetal death, preterm delivery, and perinatal mortality are reported to be higher in pregnant women with HEV infection. Alteration in the steroid hormone levels show high incidence of FHF (Fulminant Hepatic Failure) with high mortality in hepatitis E during pregnancy. The present study is designed to look for the association between ESR (Estrogen Receptor)-beta gene polymorphism for Alu I restriction site and pregnancy outcome. The study group comprised of 142 pregnant women with HEV infection in third trimester, 103 AVH (Acute Viral Hepatitis) cases and 39 ALF (Acute Liver Failure) cases. The control group comprised of 142, age and gestation matched healthy pregnant women with no obstetrics and medical complications. The inclusion criteria for the study group are pregnant women in third trimester with positivity to HEV IgM and/or HEV RNA in the age group of 18-40 years. Genomic DNA is extracted from peripheral blood leukocytes using DNA extraction kit according to the manufacturer’s instructions. The polymorphism study is done by using ESR2 specific primers and its genotype is determined by Alu I restriction enzyme. The occurrence of variant A allele for AluI restriction site is significantly higher in mothers with HEV infection who had preterm (25%) than full term delivery (10%) with OR 2.989 (95% CI = 1.265-8.084, p<0.05) and low birth weight (26.6%) than average birth weight (6.3%) babies with OR 5.399 (95% CI= 2.01-18.26, p<0.05) in pregnant women with HEV infection. The occurrence of variant A allele of ESR beta for AluI restriction site is significantly higher in mother of low birth weight babies (23%) than average birth weight babies (5.5%) in AVH group with OR 5.056 (95% CI= 1.634-21.57, p<0.05) and preterm (40.5%) than full term (0%) delivery in ALF group (p= 0.04). The higher occurrence of variant A allele for AluI restriction site of ESR-beta gene polymorphism is found to be associated with preterm delivery and low birth weight in pregnant women with HEV infection, preterm delivery in ALF group and low birth weight babies in AVH group.