Abstract
BackgroundMultiple interrelated pathways contribute to the pathogenesis of preeclampsia, and variants in susceptibility genes may play a role among Filipinos, an ethnically distinct group with high prevalence of the disease. The objective of this study was to examine the association between variants in maternal candidate genes and the development of preeclampsia in a Philippine population.MethodsA case-control study involving 29 single nucleotide polymorphisms (SNPs) in 21 candidate genes was conducted in 150 patients with preeclampsia (cases) and 175 women with uncomplicated normal pregnancies (controls). Genotyping for the GRK4 and DRD1 gene variants was carried out using the TaqMan Assay, and all other variants were assayed using the Sequenom MassARRAY Iplex Platform. PLINK was used for SNP association testing. Multilocus association analysis was performed using multifactor dimensionality reduction (MDR) analysis.ResultsAmong the clinical factors, older age (P < 1 × 10–4), higher BMI (P < 1 × 10–4), having a new partner (P = 0.006), and increased time interval from previous pregnancy (P = 0.018) associated with preeclampsia. The MDR algorithm identified the genetic variant ACVR2A rs1014064 as interacting with age and BMI in association with preeclampsia among Filipino women.ConclusionsThe MDR algorithm identified an interaction between age, BMI and ACVR2A rs1014064, indicating that context among genetic variants and demographic/clinical factors may be crucial to understanding the pathogenesis of preeclampsia among Filipino women.
Highlights
Multiple interrelated pathways contribute to the pathogenesis of preeclampsia, and variants in susceptibility genes may play a role among Filipinos, an ethnically distinct group with high prevalence of the disease
Preeclampsia is a multifactorial disease, with both genetic and environmental factors contributing to its development
We have previously found variants of the VEGF-A and Vascular endothelial growth factor receptor 1 (VEGFR1) genes to associate with preeclampsia among Filipinos, an ethnically distinct group with high prevalence [4]
Summary
Multiple interrelated pathways contribute to the pathogenesis of preeclampsia, and variants in susceptibility genes may play a role among Filipinos, an ethnically distinct group with high prevalence of the disease. Hypertensive disorders of pregnancy account for 36.7% of all maternal deaths in the Philippines [1], which is much higher than the worldwide rate of 18% [2] Included among these hypertensive diseases affecting pregnant women is preeclampsia, a severe and diverse disorder that is associated with life-threatening multiorgan maternal complications and which causes serious feto-placental problems. It accounted for 22.5% of hypertensive patient admissions at the hospital where this study was conducted [3].
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