Common variants of the hepatocyte nuclear factor-4alpha P2 promoter are associated with type 2 diabetes in the U.K. population.
Hepatocyte nuclear factor (HNF)-4alpha is part of a transcription factor network that is key for the development and function of the beta-cell. Rare mutations in the HNF4alpha gene cause maturity-onset diabetes of the young. A number of type 2 diabetes linkage studies have found evidence of linkage...
| Hlavní autoři: | , , , , , , , , , |
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| Médium: | Journal article |
| Jazyk: | English |
| Vydáno: |
2004
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| _version_ | 1826305450968088576 |
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| author | Weedon, M Owen, K Shields, B Hitman, G Walker, M McCarthy, M Love-Gregory, L Permutt, M Hattersley, A Frayling, T |
| author_facet | Weedon, M Owen, K Shields, B Hitman, G Walker, M McCarthy, M Love-Gregory, L Permutt, M Hattersley, A Frayling, T |
| author_sort | Weedon, M |
| collection | OXFORD |
| description | Hepatocyte nuclear factor (HNF)-4alpha is part of a transcription factor network that is key for the development and function of the beta-cell. Rare mutations in the HNF4alpha gene cause maturity-onset diabetes of the young. A number of type 2 diabetes linkage studies have found evidence of linkage to 20q12-13.1 where the HNF4alpha gene is located. Two recent studies have found an association between four common variants of the alternative P2 promoter region and type 2 diabetes. These variants are in strong linkage disequilibrium, and the minor alleles define one common risk haplotype. In both studies, the risk haplotype explained a large proportion of the evidence of linkage to 20q12-13.1. We aimed to assess this haplotype in a U.K. Caucasian study of 5,256 subjects. We typed two single nucleotide polymorphisms tagging the risk haplotype (rs4810424 and rs2144908) and found evidence of association in both case-control and family-based studies; rs4810424 marginally demonstrated the stronger association with an overall estimated odds ratio of 1.15 (95% CI 1.02-1.33) (P = 0.02). The effect of the P2 haplotype on type 2 diabetes risk is less than in the initial studies, probably reflecting that these studies used 20q12-13.1-linked cases. In conclusion, we have replicated the association of the HNF4alpha P2 promoter haplotype with type 2 diabetes in a U.K. Caucasian population where there is no evidence of linkage to 20q. |
| first_indexed | 2024-03-07T06:33:03Z |
| format | Journal article |
| id | oxford-uuid:f6af944b-e2bc-4f5f-9b3d-3e319d2d7e2f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:33:03Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:f6af944b-e2bc-4f5f-9b3d-3e319d2d7e2f2022-03-27T12:36:54ZCommon variants of the hepatocyte nuclear factor-4alpha P2 promoter are associated with type 2 diabetes in the U.K. population.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f6af944b-e2bc-4f5f-9b3d-3e319d2d7e2fEnglishSymplectic Elements at Oxford2004Weedon, MOwen, KShields, BHitman, GWalker, MMcCarthy, MLove-Gregory, LPermutt, MHattersley, AFrayling, THepatocyte nuclear factor (HNF)-4alpha is part of a transcription factor network that is key for the development and function of the beta-cell. Rare mutations in the HNF4alpha gene cause maturity-onset diabetes of the young. A number of type 2 diabetes linkage studies have found evidence of linkage to 20q12-13.1 where the HNF4alpha gene is located. Two recent studies have found an association between four common variants of the alternative P2 promoter region and type 2 diabetes. These variants are in strong linkage disequilibrium, and the minor alleles define one common risk haplotype. In both studies, the risk haplotype explained a large proportion of the evidence of linkage to 20q12-13.1. We aimed to assess this haplotype in a U.K. Caucasian study of 5,256 subjects. We typed two single nucleotide polymorphisms tagging the risk haplotype (rs4810424 and rs2144908) and found evidence of association in both case-control and family-based studies; rs4810424 marginally demonstrated the stronger association with an overall estimated odds ratio of 1.15 (95% CI 1.02-1.33) (P = 0.02). The effect of the P2 haplotype on type 2 diabetes risk is less than in the initial studies, probably reflecting that these studies used 20q12-13.1-linked cases. In conclusion, we have replicated the association of the HNF4alpha P2 promoter haplotype with type 2 diabetes in a U.K. Caucasian population where there is no evidence of linkage to 20q. |
| spellingShingle | Weedon, M Owen, K Shields, B Hitman, G Walker, M McCarthy, M Love-Gregory, L Permutt, M Hattersley, A Frayling, T Common variants of the hepatocyte nuclear factor-4alpha P2 promoter are associated with type 2 diabetes in the U.K. population. |
| title | Common variants of the hepatocyte nuclear factor-4alpha P2 promoter are associated with type 2 diabetes in the U.K. population. |
| title_full | Common variants of the hepatocyte nuclear factor-4alpha P2 promoter are associated with type 2 diabetes in the U.K. population. |
| title_fullStr | Common variants of the hepatocyte nuclear factor-4alpha P2 promoter are associated with type 2 diabetes in the U.K. population. |
| title_full_unstemmed | Common variants of the hepatocyte nuclear factor-4alpha P2 promoter are associated with type 2 diabetes in the U.K. population. |
| title_short | Common variants of the hepatocyte nuclear factor-4alpha P2 promoter are associated with type 2 diabetes in the U.K. population. |
| title_sort | common variants of the hepatocyte nuclear factor 4alpha p2 promoter are associated with type 2 diabetes in the u k population |
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