Allelic variations in angiogenic pathway genes are associated with preeclampsia

OBJECTIVE: This study investigates the association of allelic variation in angiogenic pathway genes and preeclampsia. STUDY DESIGN: Data for cases with preeclampsia and term control subjects were collected prospectively. Maternal DNA was extracted, and 124 tagging single nucleotide polymorphisms in 6 genes (vascular endothelial growth factor A, B, and C; fms-like tyrosine kinase 1 and 4; endoglin) were genotyped. Multivariable logistic regression was used to evaluate the association between tagging single nucleotide polymorphisms and preeclampsia; data were controlled for age. All models were evaluated in black women and white women separately. Haplotype analyses were performed. RESULTS: We analyzed data from 606 women (489 black women [184 cases] and 117 white women [32 cases]). In black women, the fms-like tyrosine kinase 1 rs12584067 (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.01-2.36; P = .05) and rs7335588 (OR, 1.61; 95% CI, 1.06-2.43; P = .01) and the vascular endothelial growth factor C rs1485766 (OR, 1.56; 95% CI, 1.05-2.30; P = .03) and rs6838834 (OR, 1.60; 95% CI, 1.05-2.45; P = .03) single nucleotide polymorphisms were associated with preeclampsia. In white women, the fms-like tyrosine kinase 1 rs722503 (OR, 2.12; 95% CI, 1.07-4.19; P = .03), fms-like tyrosine kinase 4 rs307826 (OR, 3.06; 95% CI, 1.18-7.91; P = .01), and vascular endothelial growth factor C rs7664413 (OR, 2.04; 95% CI, 0.99-4.17; P = .04) single nucleotide polymorphisms were associated with preeclampsia. CONCLUSION: Allelic variations in the fms-like tyrosine kinase 1 and vascular endothelial growth factor C genes are associated with preeclampsia in both ethnic groups.