Variants of HSD11B2 gene in hypertensive disorders of pregnancy

One of the hypotheses concerning the etiology of gestational hypertension (GH) and pre-eclampsia (PE) assumes that they develop as a result of placenta malfunctioning at the early stage of pregnancy. Placental dysfunction is also associated with the decreased activity of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), which in normal pregnancy protects the fetus from the excess of maternal cortisol.

The aim of the study was to analyze the sequence of HSD11B2, a gene that encodes 11β-HSD2, searching for mutations and haplotypes associated with the increased risk of GH or PE. Those may serve as potential genetic markers of GH and PE.

The study was performed in case-control structure and included pregnant women (in third trimester) diagnosed with: GH, PE or being normotensive (control group). The research comprised DNA sequencing of HSD11B2, followed by restriction analysis (PCR-RFLP). The linkage disequilibrium analysis and haplotype-based case-control analysis were performed.

Six sequence variations were observed. Four mutations were indicated in the coding region of HSD11B2 and the other two in 3'-UTR. Two SNPs: c.468C > A and c.534G > A were found to be in total disequilibrium.

High variability in HSD11B2 sequence was indicated in the study population, but the relevance of observed SNPs to GH or PE development was not confirmed.