| Sequencing PDX1 (insulin promoter factor 1) in 1788 UK individuals found 5% had a low frequency coding variant, but these variants are not associated with Type 2 diabetes. | |
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MedLine Citation:
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PMID: 21569088 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Diabet. Med. 28, 681-684 (2011) ABSTRACT: Aim Genome-wide association studies have identified > 30 common variants associated with Type 2 diabetes (> 5% minor allele frequency). These variants have small effects on individual risk and do not account for a large proportion of the heritable component of the disease. Monogenic forms of diabetes are caused by mutations that occur in < 1:2000 individuals and follow strict patterns of inheritance. In contrast, the role of low frequency genetic variants (minor allele frequency 0.1-5%) in Type 2 diabetes is not known. The aim of this study was to assess the role of low frequency PDX1 (also called IPF1) variants in Type 2 diabetes. Methods We sequenced the coding and flanking intronic regions of PDX1 in 910 patients with Type 2 diabetes and 878 control subjects. Results We identified a total of 26 variants that occurred in 5.3% of individuals, 14 of which occurred once. Only D76N occurred in > 1%. We found no difference in carrier frequency between patients (5.7%) and control subjects (5.0%) (P = 0.46). There were also no differences between patients and control subjects when analyses were limited to subsets of variants. The strongest subset were those variants in the DNA binding domain where all five variants identified were only found in patients (P = 0.06). Conclusion Approximately 5% of UK individuals carry a PDX1 variant, but there is no evidence that these variants, either individually or cumulatively, predispose to Type 2 diabetes. Further studies will need to consider strategies to assess the role of multiple variants that occur in < 1 in 1000 individuals. |
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Authors:
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E L Edghill; A Khamis; M N Weedon; M Walker; G A Hitman; M I McCarthy; K R Owen; S Ellard; A T Hattersley; T M Frayling |
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Publication Detail:
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Type: JOURNAL ARTICLE |
Journal Detail:
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Title: Diabetic medicine : a journal of the British Diabetic Association Volume: 28 ISSN: 1464-5491 ISO Abbreviation: - Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-5-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8500858 Medline TA: Diabet Med Country: - |
Other Details:
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Languages: ENG Pagination: 681-684 Citation Subset: - |
Copyright Information:
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© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK. |
Affiliation:
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Institute of Biomedical and Clinical Science Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter Institute of Cellular Medicine, Newcastle University Department of Diabetes and Metabolism, Barts and the London NHS Trust and School of Medicine and Dentistry, London Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford Oxford NIHR Biomedical Research Centre, Churchill Hospital Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. |
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