Association studies of insulin receptor substrate 1 gene (IRS1) variants in type 2 diabetes samples enriched for family history and early age of onset.
The gene encoding insulin receptor substrate-1 (IRS1) represents a strong biological candidate for a contributory role in type 2 diabetes susceptibility. Indeed, functional studies have implicated the G971R variant, and a recent meta-analysis of 27 association studies suggested that carriage of 971R...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2004
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| _version_ | 1826275814592741376 |
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| author | Zeggini, E Parkinson, J Halford, S Owen, K Frayling, T Walker, M Hitman, G Levy, J Sampson, M Feskens, E Hattersley, A McCarthy, M |
| author_facet | Zeggini, E Parkinson, J Halford, S Owen, K Frayling, T Walker, M Hitman, G Levy, J Sampson, M Feskens, E Hattersley, A McCarthy, M |
| author_sort | Zeggini, E |
| collection | OXFORD |
| description | The gene encoding insulin receptor substrate-1 (IRS1) represents a strong biological candidate for a contributory role in type 2 diabetes susceptibility. Indeed, functional studies have implicated the G971R variant, and a recent meta-analysis of 27 association studies suggested that carriage of 971R was associated with a 25% increase in disease risk. However, this association has not been evaluated in large samples. The present study genotyped the P512A and G971R IRS1 variants in 971 U.K. type 2 diabetic subjects ascertained for strong family history and/or early onset, as well as 1,257 control subjects matched by ethnicity. There was no evidence for association with type 2 diabetes for either variant. (For example, the odds ratio [OR] for carriage of 971R was 1.11 [95% CI 0.86-1.44, P = 0.44]) An updated meta-analysis (31 studies: 5,104 case and 7,418 control subjects) remained significant for the G971R association (P = 0.025), albeit with a diminished OR (1.15 [95% CI 1.02-1.31]). Additional studies of IRS1 variation will be required to obtain a robust estimate of the overall contribution of IRS1 variation to type 2 diabetes susceptibility, but the current study suggests that previous studies have overestimated the magnitude of this effect. |
| first_indexed | 2024-03-06T23:04:32Z |
| format | Journal article |
| id | oxford-uuid:63528411-90d8-4d13-9c33-31e1fb93b596 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:04:32Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:63528411-90d8-4d13-9c33-31e1fb93b5962022-03-26T18:12:11ZAssociation studies of insulin receptor substrate 1 gene (IRS1) variants in type 2 diabetes samples enriched for family history and early age of onset.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:63528411-90d8-4d13-9c33-31e1fb93b596EnglishSymplectic Elements at Oxford2004Zeggini, EParkinson, JHalford, SOwen, KFrayling, TWalker, MHitman, GLevy, JSampson, MFeskens, EHattersley, AMcCarthy, MThe gene encoding insulin receptor substrate-1 (IRS1) represents a strong biological candidate for a contributory role in type 2 diabetes susceptibility. Indeed, functional studies have implicated the G971R variant, and a recent meta-analysis of 27 association studies suggested that carriage of 971R was associated with a 25% increase in disease risk. However, this association has not been evaluated in large samples. The present study genotyped the P512A and G971R IRS1 variants in 971 U.K. type 2 diabetic subjects ascertained for strong family history and/or early onset, as well as 1,257 control subjects matched by ethnicity. There was no evidence for association with type 2 diabetes for either variant. (For example, the odds ratio [OR] for carriage of 971R was 1.11 [95% CI 0.86-1.44, P = 0.44]) An updated meta-analysis (31 studies: 5,104 case and 7,418 control subjects) remained significant for the G971R association (P = 0.025), albeit with a diminished OR (1.15 [95% CI 1.02-1.31]). Additional studies of IRS1 variation will be required to obtain a robust estimate of the overall contribution of IRS1 variation to type 2 diabetes susceptibility, but the current study suggests that previous studies have overestimated the magnitude of this effect. |
| spellingShingle | Zeggini, E Parkinson, J Halford, S Owen, K Frayling, T Walker, M Hitman, G Levy, J Sampson, M Feskens, E Hattersley, A McCarthy, M Association studies of insulin receptor substrate 1 gene (IRS1) variants in type 2 diabetes samples enriched for family history and early age of onset. |
| title | Association studies of insulin receptor substrate 1 gene (IRS1) variants in type 2 diabetes samples enriched for family history and early age of onset. |
| title_full | Association studies of insulin receptor substrate 1 gene (IRS1) variants in type 2 diabetes samples enriched for family history and early age of onset. |
| title_fullStr | Association studies of insulin receptor substrate 1 gene (IRS1) variants in type 2 diabetes samples enriched for family history and early age of onset. |
| title_full_unstemmed | Association studies of insulin receptor substrate 1 gene (IRS1) variants in type 2 diabetes samples enriched for family history and early age of onset. |
| title_short | Association studies of insulin receptor substrate 1 gene (IRS1) variants in type 2 diabetes samples enriched for family history and early age of onset. |
| title_sort | association studies of insulin receptor substrate 1 gene irs1 variants in type 2 diabetes samples enriched for family history and early age of onset |
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