Large-scale studies of the association between variation at the TNF/LTA locus and susceptibility to type 2 diabetes.
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-synon...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2005
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| _version_ | 1826293250351169536 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Zeggini, E |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T03:27:13Z |
| format | Journal article |
| id | oxford-uuid:b9775116-e0f8-4951-ab70-d4136f9bb1e8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:27:13Z |
| publishDate | 2005 |
| record_format | dspace |
| spelling | oxford-uuid:b9775116-e0f8-4951-ab70-d4136f9bb1e82022-03-27T05:03:05ZLarge-scale studies of the association between variation at the TNF/LTA locus and susceptibility to type 2 diabetes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b9775116-e0f8-4951-ab70-d4136f9bb1e8EnglishSymplectic Elements at Oxford2005Zeggini, EGroves, CParkinson, JRHalford, SOwen, KFrayling, TWalker, MHitman, GLevy, JO'Rahilly, SHattersley, AMcCarthy, MAIMS/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. |
| spellingShingle | 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 Large-scale studies of the association between variation at the TNF/LTA locus and susceptibility to type 2 diabetes. |
| title | Large-scale studies of the association between variation at the TNF/LTA locus and susceptibility to type 2 diabetes. |
| title_full | Large-scale studies of the association between variation at the TNF/LTA locus and susceptibility to type 2 diabetes. |
| title_fullStr | Large-scale studies of the association between variation at the TNF/LTA locus and susceptibility to type 2 diabetes. |
| title_full_unstemmed | Large-scale studies of the association between variation at the TNF/LTA locus and susceptibility to type 2 diabetes. |
| title_short | Large-scale studies of the association between variation at the TNF/LTA locus and susceptibility to type 2 diabetes. |
| title_sort | large scale studies of the association between variation at the tnf lta locus and susceptibility to type 2 diabetes |
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