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

Zeggini, E; Groves, C; Parkinson, JR; Halford, S; Owen, K; Frayling, T; Walker, M; Hitman, G; Levy, J; O'Rahilly, S; Hattersley, A; McCarthy, M

Journal article

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

Abstract:: AIMS/HYPOTHESIS: The proinflammatory cytokine TNF-alpha has been implicated in the pathogenesis of insulin resistance and type 2 diabetes, and variation in the gene encoding TNF-alpha (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.

Publication status:: Published

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APA Style

Zeggini, E., Groves, C., Parkinson, J. R., Halford, S., Owen, K., Frayling, T., Walker, M., Hitman, G., Levy, J., O'Rahilly, S., Hattersley, A., & McCarthy, M. (2005). Large-scale studies of the association between variation at the TNF/LTA locus and susceptibility to type 2 diabetes. Diabetologia, 48(10), 2013–2017.

MLA Style

Zeggini, E., et al. “Large-Scale Studies of the Association between Variation at the TNF/LTA Locus and Susceptibility to Type 2 Diabetes.” Diabetologia, vol. 48, no. 10, 2005, pp. 2013–17.

Chicago Style

Zeggini, E, C Groves, JR Parkinson, S Halford, K Owen, T Frayling, M Walker, et al. 2005. “Large-Scale Studies of the Association between Variation at the TNF/LTA Locus and Susceptibility to Type 2 Diabetes.” Diabetologia 48 (10): 2013–17.
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