Genetic variation in tumour necrosis factor and lymphotoxin is not associated with endometriosis in an Australian sample.
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 (r(2) = 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.
Zhao
Zhen Zhen
ZZ
Molecular Epidemiology, Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane, Queensland 4029, Australia. zhen.zhao@qimr.edu.au
Nyholt
Dale R
DR
Le
Lien
L
Thomas
Shane
S
Engwerda
Christian
C
Randall
Louise
L
Treloar
Susan A
SA
Montgomery
Grant W
GW
D001315:Australia; D001483:Base Sequence; D004715:Endometriosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha