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Hum. Reprod. Advance Access originally published online on June 26, 2007
Human Reproduction 2007 22(9):2389-2397; doi:10.1093/humrep/dem182
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Genetic variation in tumour necrosis factor and lymphotoxin is not associated with endometriosis in an Australian sample

Zhen Zhen Zhao1,4, Dale R. Nyholt2, Lien Le1, Shane Thomas1, Christian Engwerda3, Louise Randall3, Susan A. Treloar2 and Grant W. Montgomery1

1 Molecular Epidemiology, Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane, Queensland 4029, Australia 2 Genetic Epidemiology, Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane, Queensland 4029, Australia 3 Immunology and Infection Laboratories, Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane, Queensland 4029, Australia

4 Correspondence address. Tel: +61-7-38453742; Fax: +61-7-33620101; E-mail: zhen.zhao{at}qimr.edu.au

BACKGROUND: Tumour necrosis factor (TNF) is a pleiotropic cytokine with a wide range of immunoregulatory effects. Variation in the promoter region of TNF and the neighbouring lymphotoxin alpha (LTA) gene might be associated with endometriosis.

METHODS: We examined the association between endometriosis and common single-nucleotide polymorphisms (SNPs) or haplotypes in the TNF/LTA region in an Australian sample by analysing 26 SNPs in 958 endometriosis cases and 959 unrelated controls. We selected functional SNPs in the coding and the promoter region of the TNF gene and HapMap tagging SNPs and typed them on a Sequenom MassARRAY platform. A key SNP (rs1800630) in the promoter region typed in previous studies did not give reliable results. Therefore, we also examined a statistically identical (r2 = 1) SNP (siSNP) (rs2844482), identified using the web based program ssSNPer.

RESULTS: Genotype completion rate was 99.5% for SNPs spanning a region of 15.5 kb across the TNF/LTA locus. There was no evidence for association between endometriosis and TNF/LTA SNPs or SNP haplotypes in our case–control study.

CONCLUSIONS: Our data suggest both TNF and LTA genes are not major susceptibility genes for endometriosis.

Key words: endometriosis/tumour necrosis factor/single-nucleotide polymorphism/haplotype/lymphotoxin alpha

Submitted on November 21, 2006; resubmitted on May 16, 2007; accepted on May 25, 2007.


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