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The functional "KL-VS" variant of KLOTHO is not associated with type 2 diabetes in 5028 UK Caucasians
BACKGROUND: Klotho has an important role in insulin signalling and the development of ageing-like phenotypes in mice. The common functional "KL-VS" variant in the KLOTHO (KL) gene is associated with longevity in humans but its role in type 2 diabetes is not known. We performed a large case...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2006
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1534014/ https://www.ncbi.nlm.nih.gov/pubmed/16753056 http://dx.doi.org/10.1186/1471-2350-7-51 |
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author | Freathy, Rachel M Weedon, Michael N Melzer, David Shields, Beverley Hitman, Graham A Walker, Mark McCarthy, Mark I Hattersley, Andrew T Frayling, Timothy M |
author_facet | Freathy, Rachel M Weedon, Michael N Melzer, David Shields, Beverley Hitman, Graham A Walker, Mark McCarthy, Mark I Hattersley, Andrew T Frayling, Timothy M |
author_sort | Freathy, Rachel M |
collection | PubMed |
description | BACKGROUND: Klotho has an important role in insulin signalling and the development of ageing-like phenotypes in mice. The common functional "KL-VS" variant in the KLOTHO (KL) gene is associated with longevity in humans but its role in type 2 diabetes is not known. We performed a large case-control and family-based study to test the hypothesis that KL-VS is associated with type 2 diabetes in a UK Caucasian population. METHODS: We genotyped 1793 cases, 1619 controls and 1616 subjects from 509 families for the single nucleotide polymorphism (SNP) F352V (rs9536314) that defines the KL-VS variant. Allele and genotype frequencies were compared between cases and controls. Family-based analysis was used to test for over- or under-transmission of V352 to affected offspring. RESULTS: Despite good power to detect odds ratios of 1.2, there were no significant associations between alleles or genotypes and type 2 diabetes (V352 allele: odds ratio = 0.96 (0.84–1.09)). Additional analysis of quantitative trait data in 1177 healthy control subjects showed no association of the variant with fasting insulin, glucose, triglycerides, HDL- or LDL-cholesterol (all P > 0.05). However, the HDL-cholesterol levels observed across the genotype groups showed a similar, but non-significant, pattern to previously reported data. CONCLUSION: This is the first large-scale study to examine the association between common functional variation in KL and type 2 diabetes risk. We have found no evidence that the functional KL-VS variant is a risk factor for type 2 diabetes in a large UK Caucasian case-control and family-based study. |
format | Text |
id | pubmed-1534014 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-15340142006-08-09 The functional "KL-VS" variant of KLOTHO is not associated with type 2 diabetes in 5028 UK Caucasians Freathy, Rachel M Weedon, Michael N Melzer, David Shields, Beverley Hitman, Graham A Walker, Mark McCarthy, Mark I Hattersley, Andrew T Frayling, Timothy M BMC Med Genet Research Article BACKGROUND: Klotho has an important role in insulin signalling and the development of ageing-like phenotypes in mice. The common functional "KL-VS" variant in the KLOTHO (KL) gene is associated with longevity in humans but its role in type 2 diabetes is not known. We performed a large case-control and family-based study to test the hypothesis that KL-VS is associated with type 2 diabetes in a UK Caucasian population. METHODS: We genotyped 1793 cases, 1619 controls and 1616 subjects from 509 families for the single nucleotide polymorphism (SNP) F352V (rs9536314) that defines the KL-VS variant. Allele and genotype frequencies were compared between cases and controls. Family-based analysis was used to test for over- or under-transmission of V352 to affected offspring. RESULTS: Despite good power to detect odds ratios of 1.2, there were no significant associations between alleles or genotypes and type 2 diabetes (V352 allele: odds ratio = 0.96 (0.84–1.09)). Additional analysis of quantitative trait data in 1177 healthy control subjects showed no association of the variant with fasting insulin, glucose, triglycerides, HDL- or LDL-cholesterol (all P > 0.05). However, the HDL-cholesterol levels observed across the genotype groups showed a similar, but non-significant, pattern to previously reported data. CONCLUSION: This is the first large-scale study to examine the association between common functional variation in KL and type 2 diabetes risk. We have found no evidence that the functional KL-VS variant is a risk factor for type 2 diabetes in a large UK Caucasian case-control and family-based study. BioMed Central 2006-06-05 /pmc/articles/PMC1534014/ /pubmed/16753056 http://dx.doi.org/10.1186/1471-2350-7-51 Text en Copyright © 2006 Freathy et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Freathy, Rachel M Weedon, Michael N Melzer, David Shields, Beverley Hitman, Graham A Walker, Mark McCarthy, Mark I Hattersley, Andrew T Frayling, Timothy M The functional "KL-VS" variant of KLOTHO is not associated with type 2 diabetes in 5028 UK Caucasians |
title | The functional "KL-VS" variant of KLOTHO is not associated with type 2 diabetes in 5028 UK Caucasians |
title_full | The functional "KL-VS" variant of KLOTHO is not associated with type 2 diabetes in 5028 UK Caucasians |
title_fullStr | The functional "KL-VS" variant of KLOTHO is not associated with type 2 diabetes in 5028 UK Caucasians |
title_full_unstemmed | The functional "KL-VS" variant of KLOTHO is not associated with type 2 diabetes in 5028 UK Caucasians |
title_short | The functional "KL-VS" variant of KLOTHO is not associated with type 2 diabetes in 5028 UK Caucasians |
title_sort | functional "kl-vs" variant of klotho is not associated with type 2 diabetes in 5028 uk caucasians |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1534014/ https://www.ncbi.nlm.nih.gov/pubmed/16753056 http://dx.doi.org/10.1186/1471-2350-7-51 |
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