PHLDA2 gene polymorphisms and risk of HELLP syndrome and severe preeclampsia

Objective: Pleckstrin homology-like domain, family A, member 2 (PHLDA2) is a maternally expressed imprinted gene. Loss of imprinting in PHLDA2 is associated with abnormal placental development and fetal growth restriction. Our objective was to determine whether genetic variation in PHLDA2 is also associated with risk of HELLP syndrome and preeclampsia (PE) with severe features.

Study design: Case (n = 162) and control (n = 33) mother-father-child triads were recruited using an internet-based method. Medical records were reviewed to verify clinical diagnosis of self-reported cases. DNA was genotyped for three polymorphisms in the PHLDA2 gene using TaqMan assays: rs13390, rs1056819, rs2583435.

Main outcome measures: To examine the association between minor alleles and haplotypes with HELLP syndrome and PE with severe features, relative risks and 95% confidence intervals were estimated using log-linear models, adjusting for the correlation between familial genotypes, using HAPLIN.

Results: There was no association identified between PHLDA2 gene polymorphisms or haplotypes and HELLP syndrome and PE with severe features. No parent-of-origin effects were observed.

Conclusion: Genetic variation in the PHLDA2 gene is not associated with HELLP syndrome or PE with severe features.