Mol. Hum. Reprod. Advance Access published online on December 5, 2008
Molecular Human Reproduction, doi:10.1093/molehr/gan076
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Vascular endothelial growth factor genotypes and haplotypes are associated with preeclampsia but not with gestational hypertension
aDepartment of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil bDepartment of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 13081-970, Campinas, SP, Brazil cDepartment of Gynecology and Obstetrics, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil dDepartment of Genetics, University Hospital of Medicine School of Ribeiráo Preto, University of Sáo Paulo, Ribeiráo Preto, SP, Brazil
* Corresponding author : Jose Eduardo Tanus-Santos, MD, PhD., Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirao Preto, SP, Brazil, FAX: +55 16 3633 2301, Phone: +55 16 3602 3163, E-mail: tanus{at}fmrp.usp.br
Vascular endothelial growth factor (VEGF) is relevant for normal pregnancy, and abnormalities in VEGF functions areassociated with hypertensive disorders of pregnancy. Because there are few studies on how VEGF genetic polymorphisms affect susceptibility to preeclampsia, and no studies on how they affect susceptibility to gestational hypertension, we compared VEGF genotype and haplotype distributions in normotensive and hypertensive pregnancies. Genotypes and haplotypes for VEGF polymorphisms (C-2578A, G-1154A and G-634C) were determined in 303 pregnant women (108 healthy pregnant, HP; 101 with gestational hypertension, GH; and 94 with preeclampsia, PE). When white and non-white pregnant women were considered together, no significant differences were found in the distributions of VEGF genotypes or haplotypes (P>0.05) in the three groups. However, with only white subjects, significant differences were found in genotypes distributions for two (C-2578A and G-634C) VEGF polymorphisms (both P<0.05) between the HP and the PE groups. Importantly, the haplotype including the variants C-2578, G-1154, and C-634, which isassociated with higher VEGF gene expression, was less common in the PE group compared with the HP group (4% versus 16%; P=0.0047). However, we found no significant differences in VEGF haplotypes distributions when HP and GH groups were compared (P>0.05). These findings suggest a protective effect for the "C-2578, G-1154, and C-634" haplotype against the development of preeclampsia, but no major effects of VEGF gene variants on susceptibility to gestational hypertension.
Key Words: gestational hypertension/haplotypes/preeclampsia/vascular endothelial growth factor/VEGF
Submitted on October 14, 2008; resubmitted on November 25, 2008; accepted on December 1, 2008.