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Hum. Reprod. Advance Access published online on March 3, 2005
Human Reproduction, doi:10.1093/humrep/deh852
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Human Reproduction © European Society of Human Reproduction and Embryology 2005; all rights reserved
Received December 23, 2004
Revised February 8, 2005
Accepted February 16, 2005

Article

The vascular endothelial growth factor (VEGF) +405G>C 5'-untranslated region polymorphism and increased risk of endometriosis in South Indian women: a case control study

Manjula Bhanoori 1, K. Arvind Babu 1, N.G. Pavankumar Reddy 1, K. Lakshmi Rao 1, Krina Zondervan 2, Mamata Deenadayal 3, Stephen Kennedy 4, and S. Shivaji 5*

1 Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India
2 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
3 Infertility Institute and Research Centre, Hyderabad, India
4 Nuffield Department of Obstetrics & Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford, UK
5 Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India, Nuffield Department of Obstetrics & Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford, UK

* To whom correspondence should be addressed.
S. Shivaji, E-mail: shivas{at}ccmb.res.in


  Abstract

BACKGROUND: Vascular endothelial growth factor (VEGF), a major mediator of angiogenesis and vascular permeability, is known to play a key role in the pathophysiology of endometriosis. METHODS AND RESULTS: The single nucleotide polymorphisms, -460C>T and +405G>C, in the 5'-untranslated region of the VEGF gene were tested for association in a case-control study of 215 affected women and 210 women with no evidence of disease. All the women were of South Indian origin and ascertained from the same infertility clinic. The genotype and allele frequencies of the -460C>T polymorphism did not differ significantly between cases and controls. In contrast, the genotype (P=0.002) and allele (P=0.001) frequencies of the +405G>C polymorphism showed a significant difference between cases and controls. The +405 GG genotype was found more often in patients with an endometrioma >3 cm compared to controls. The frequency of the -460T/+405C haplotype (P=0.016) was significantly lower in affected women compared to controls. CONCLUSIONS: The -460T/+405C haplotype in the VEGF gene, which is associated with lower promoter activity, was significantly less common in women with endometriosis than in controls. These data suggest that the +405G allele may influence the likelihood of a woman developing the disease.

Keywords: endometriosis; polymorphism; VEGF.
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