Mol. Hum. Reprod. Advance Access published online on July 23, 2008
Molecular Human Reproduction, doi:10.1093/molehr/gan043
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Polymorphisms in the vascular endothelial growth factor gene and the risk of familial endometriosis
1Molecular Epidemiology Genetic Epidemiology Laboratories, Queensland Institute of Medical Research, Brisbane, Queensland, Australia 2Genetic Epidemiology Laboratories, Queensland Institute of Medical Research, Brisbane, Queensland, Australia
3 To whom correspondence should be addressed at: Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia. E-mail: Zhen.Zhao{at}qimr.edu.au
Vascular endothelial growth factor (VEGF) is an endothelial cell-specific angiogenic protein suspected to be involved in the pathogenesis of endometriosis by establishing a new blood supply to the human exfoliated endometrium. Several transcription factor-binding sites are found in the VEGF 5’-untranslated region (UTR) and variation within the region increases transcriptional activity. Six previous studies which tested between 1 and 3 single nucleotide polymorphisms (SNPs) in samples comprising 105-215 cases and 100-219 controls have produced conflicting evidence for association between the SNPs in the VEGF region and endometriosis. To further investigate the reported association between VEGF variants and endometriosis, we tested the four VEGF polymorphisms (-2578 A/C, rs699947; -460 T/C, rs833061; +405 G/C, rs2010963 and +936 C/T, rs3025039) in a large Australian sample of 958 familial endometriosis cases and 959 controls. We also conducted a literature-based review of all relevant association studies of these VEGF SNPs in endometriosis and performed a meta-analysis. There was no evidence for association between endometriosis and the VEGF polymorphisms genotyped in our study. Combined association results from a meta-analysis did not provide any evidence for either genotypic or allelic association with endometriosis. Our detailed review and meta-analysis of the VEGF polymorphisms suggests genotyping assay problems may underlie the previously reported associations between VEGF variants and endometriosis.
Key Words: endometriosis/VEGF/polymorphism/meta-analysis
Submitted on May 25, 2008; resubmitted on July 16, 2008; accepted on July 21, 2008.
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