Non-additive effects of ACVR2A in preeclampsia in a Philippine population

Abstract

BACKGROUND: 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. 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. METHODS: A 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. RESULTS: Among 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. CONCLUSIONS: The 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.