Large-scale studies of the association between variation at the TNF/LTA locus and susceptibility to type 2 diabetes
| Autor: | Mark I. McCarthy, Graham A. Hitman, Andrew T. Hattersley, Parkinson Jrc., C J Groves, Stephen O'Rahilly, Eleftheria Zeggini, Mark Walker, S. Halford, Katharine R. Owen, J C Levy, Timothy M. Frayling |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male Linkage disequilibrium Genotype Endocrinology Diabetes and Metabolism Locus (genetics) Type 2 diabetes Biology Polymorphism Single Nucleotide Linkage Disequilibrium Proinflammatory cytokine Insulin resistance Gene Frequency Diabetes mellitus Internal Medicine medicine Humans Age of Onset Genotyping Lymphotoxin-alpha Aged Genetics Tumor Necrosis Factor-alpha Genetic Variation Middle Aged medicine.disease United Kingdom Diabetes Mellitus Type 2 Immunology Female |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|