Mol. Hum. Reprod. Advance Access originally published online on December 5, 2008
Molecular Human Reproduction 2009 15(2):115-120; doi:10.1093/molehr/gan076
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Vascular endothelial growth factor genotypes and haplotypes are associated with pre-eclampsia but not with gestational hypertension
1Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirao Preto, SP, Brazil 2Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 13081-970 Campinas, SP, Brazil 3Department of Gynecology and Obstetrics, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirao Preto, SP, Brazil 4Department of Genetics, University Hospital of Medicine School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil
5 Correspondence address. Tel: +55-16-3602-3163; Fax: +55-16-3633-2301; E-mail: tanus{at}fmrp.usp.br
Vascular endothelial growth factor (VEGF) is relevant for normal pregnancy, and abnormalities in VEGF functions are associated with hypertensive disorders of pregnancy. Because there are few studies on how VEGF genetic polymorphisms affect susceptibility to pre-eclampsia (PE), and no studies on how they affect susceptibility to gestational hypertension (GH), 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 GH and 94 with 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 is associated 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 the 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 PE, but no major effects of VEGF gene variants on susceptibility to GH.
Key words: gestational hypertension/haplotypes/pre-eclampsia/vascular endothelial growth factor/VEGF
Submitted on October 14, 2008; resubmitted on November 25, 2008; accepted on December 1, 2008.