Title : Association between hypertension susceptibility gene polymorphism and severe preeclampsia
Abstract:
Introduction: Preeclampsia (PE) is a life-threatening pregnancy-specific disorder and results in maternal and fetal morbidity and mortality. Numerous epidemiological studies indicate that PE has a significant heritable component (more than 60%). The present study aimed to explore the association between hypertension (HT) susceptibility gene polymorphisms and severe PE in a population of Caucasian origin.
Materials and methods: A case-control study consisting of 217 pregnant women with severe PE and 498 women with uncomplicated pregnancies was performed. The rs1799945 of the HFE gene, rs805303 of the BAG6 gene, rs4387287 of the OBFC1 gene, rs633185 of the ARHGAP42 gene, rs2681472 of the ATP2B1 gene polymorphisms were genotyped and were also associated with the HT according to the genome-wide association studies (GWAS). The PLINK v. 2.050 program was used to study the associations.
Results: All tested polymorphisms were in agreement with Hardy-Weinberg equilibrium in case/control subjects (p≥ 0.05). A significantly increased risk of severe PE was determined to be associated with the rs1799945 GG genotype in recessive genetic model (OR= 2.41; 95% CI= 1.06 – 5.45; p= 0.03; pperm= 0.01). PE-associated polymorphic locus rs1799945 of the HFE gene have serious prediction weight (identifies the non-synonymous substitutions of the homeostatic iron regulator protein His63Asp with a “probably damaging” score, is located in the DNase-I hypersensitive sites and in the region of promoters/enhancers in the trophoblast, amnion, placenta, brain, is associated with gene expression in various parts of the reproductive and cardiovascular systems).
Conclusion: The polymorphism rs1799945 of the HFE gene is associated with severe PE in Caucasian.
