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Diabetologia
Published in: Diabetologia 10/2005

01-10-2005 | Article

Large-scale studies of the association between variation at the TNF/LTA locus and susceptibility to type 2 diabetes

Authors: E. Zeggini, C. J. Groves, J. R. C. Parkinson, S. Halford, K. R. Owen, T. M. Frayling, M. Walker, G. A. Hitman, J. C. Levy, S. O’Rahilly, A. T. Hattersley, M. I. McCarthy

Published in: Diabetologia | Issue 10/2005

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Abstract

Aims/hypothesis

The proinflammatory cytokine TNF-α has been implicated in the pathogenesis of insulin resistance and type 2 diabetes, and variation in the gene encoding TNF-α (TNF) has shown inconsistent associations with susceptibility to both conditions. Additionally, the coding non-synonymous variant T60N in the neighbouring LTA gene has been reported to be associated with type 2 diabetes. The present study aimed to obtain a robust assessment of the role of variation in the tightly linked TNF/LTA region in diabetes susceptibility by genotyping TNF and LTA variants in large case-control resources.

Materials and methods

The G-308A and G-238A TNF promoter variants and the LTA T60N polymorphism were genotyped in two UK case samples that were ascertained for positive family history and/or early onset of type 2 diabetes (combined n=858) and in 1,257 ethnically matched controls.

Results

There were no significant associations between the T60N, G-308A or G-238A genotype and type 2 diabetes in the combined analysis (exact Cochran–Mantel–Haenszel statistic for ordered genotypes for T60N, p=0.69; for G-308A, p=0.51; for G-238A, p=0.16).

Conclusions/interpretation

The present study, one of the largest association analyses yet reported at this locus, provides no evidence that the specific TNF or LTA variants examined influence susceptibility to type 2 diabetes. More comprehensive studies of the TNF/LTA locus in substantially larger sample sets are required to establish whether genome sequence variation at this locus truly influences susceptibility to type 2 diabetes.
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Metadata
Title
Large-scale studies of the association between variation at the TNF/LTA locus and susceptibility to type 2 diabetes
Authors
E. Zeggini
C. J. Groves
J. R. C. Parkinson
S. Halford
K. R. Owen
T. M. Frayling
M. Walker
G. A. Hitman
J. C. Levy
S. O’Rahilly
A. T. Hattersley
M. I. McCarthy
Publication date
01-10-2005
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 10/2005
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-005-1902-4

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