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.

Key words: angiogenesis, gene, preeclampsia, sFlt