VEGF plays a crucial role in placental vasculogenesis. VEGF imbalance has been implicated in the pathogenesis of preeclampsia and other perinatal complications. Previous studies suggest that SNPs in the VEGF gene contribute to abnormal vascular function in various medical conditions. Our objective was to compare the distribution of VEGF gene SNPs between unexplained SB and control in a well-characterized cohort.
Placentas were obtained from SB and healthy controls. Following an extensive workup, SB were classified as unexplained using a modified version of the Wigglesworth system. Placental DNA was extracted using Qiagen kits, and evaluated for six VEGF SNPs (−2578C/A, −936C/T, −1154 G/A, −634 G/C, −460C/T, −405G/C) by real time PCR using specific taqman probes. The genotype and allelic distributions were analyzed by Chi-square (p<0.05 was considered statistically significant).
Placentas from 33 unexplained SB and 33 healthy controls were included. All SNPs were in Hardy-Weinberg equilibrium. Genotypes −2578 C/A and −460 C/T were significantly less frequent in SB compared to controls (p<0.005). VEGF-460 T allele occurred more frequently in SB placentas compared with controls (p=0.02). No significant associations between SB and the genotypic or allelic frequencies of the other SNPs were found.
Genotypes −2578 C/A and −460 C/T are protective, but the VEGF-460 T allele is associated with unexplained stillbirths. A role for placental VEGF imbalance in the etiology of stillbirths is also supported by the well-characterized association between these SNPs and altered VEGF production. Further studies focusing on VEGF for prediction and/or prevention of stillbirths are warranted.
© 2008 Mosby, Inc. Published by Elsevier Inc. All rights reserved.