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

Lookup NU author(s): Professor Mark Walker


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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. © Springer-Verlag 2005.

Publication metadata

Author(s): Zeggini E, Groves CJ, Parkinson JRC, Halford S, Owen KR, Frayling TM, Walker M, Hitman GA, Levy JC, O'Rahilly S, Hattersley AT, McCarthy MI

Publication type: Article

Publication status: Published

Journal: Diabetologia

Year: 2005

Volume: 48

Issue: 10

Pages: 2013-2017

Print publication date: 01/10/2005

ISSN (print): 0012-186X

ISSN (electronic): 1432-0428

Publisher: Springer


DOI: 10.1007/s00125-005-1902-4

PubMed id: 16132956


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