The functional "KL-VS" variant of KLOTHO is not associated with type 2 diabetes in 5028 UK Caucasians
<p style="text-align:justify;"> <b>Background:</b> 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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
BioMed Central
2006
|
| _version_ | 1797075349402550272 |
|---|---|
| author | Freathy, R Weedon, M Melzer, D Shields, B Hitman, G Walker, M McCarthy, M Hattersley, A Frayling, T |
| author_facet | Freathy, R Weedon, M Melzer, D Shields, B Hitman, G Walker, M McCarthy, M Hattersley, A Frayling, T |
| author_sort | Freathy, R |
| collection | OXFORD |
| description | <p style="text-align:justify;"> <b>Background:</b> 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.<br/><br/> <b>Methods:</b> 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.<br/><br/> <b>Results:</b> 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.<br/><br/> <b>Conclusion:</b> 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. </p> |
| first_indexed | 2024-03-06T23:49:12Z |
| format | Journal article |
| id | oxford-uuid:7202bbc9-0608-4dc7-90be-2341bdc7ef8e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:49:12Z |
| publishDate | 2006 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:7202bbc9-0608-4dc7-90be-2341bdc7ef8e2022-03-26T19:47:24ZThe functional "KL-VS" variant of KLOTHO is not associated with type 2 diabetes in 5028 UK CaucasiansJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7202bbc9-0608-4dc7-90be-2341bdc7ef8eEnglishSymplectic Elements at OxfordBioMed Central2006Freathy, RWeedon, MMelzer, DShields, BHitman, GWalker, MMcCarthy, MHattersley, AFrayling, T <p style="text-align:justify;"> <b>Background:</b> 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.<br/><br/> <b>Methods:</b> 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.<br/><br/> <b>Results:</b> 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.<br/><br/> <b>Conclusion:</b> 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. </p> |
| spellingShingle | Freathy, R Weedon, M Melzer, D Shields, B Hitman, G Walker, M McCarthy, M Hattersley, A Frayling, T 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 |
| work_keys_str_mv | AT freathyr thefunctionalklvsvariantofklothoisnotassociatedwithtype2diabetesin5028ukcaucasians AT weedonm thefunctionalklvsvariantofklothoisnotassociatedwithtype2diabetesin5028ukcaucasians AT melzerd thefunctionalklvsvariantofklothoisnotassociatedwithtype2diabetesin5028ukcaucasians AT shieldsb thefunctionalklvsvariantofklothoisnotassociatedwithtype2diabetesin5028ukcaucasians AT hitmang thefunctionalklvsvariantofklothoisnotassociatedwithtype2diabetesin5028ukcaucasians AT walkerm thefunctionalklvsvariantofklothoisnotassociatedwithtype2diabetesin5028ukcaucasians AT mccarthym thefunctionalklvsvariantofklothoisnotassociatedwithtype2diabetesin5028ukcaucasians AT hattersleya thefunctionalklvsvariantofklothoisnotassociatedwithtype2diabetesin5028ukcaucasians AT fraylingt thefunctionalklvsvariantofklothoisnotassociatedwithtype2diabetesin5028ukcaucasians AT freathyr functionalklvsvariantofklothoisnotassociatedwithtype2diabetesin5028ukcaucasians AT weedonm functionalklvsvariantofklothoisnotassociatedwithtype2diabetesin5028ukcaucasians AT melzerd functionalklvsvariantofklothoisnotassociatedwithtype2diabetesin5028ukcaucasians AT shieldsb functionalklvsvariantofklothoisnotassociatedwithtype2diabetesin5028ukcaucasians AT hitmang functionalklvsvariantofklothoisnotassociatedwithtype2diabetesin5028ukcaucasians AT walkerm functionalklvsvariantofklothoisnotassociatedwithtype2diabetesin5028ukcaucasians AT mccarthym functionalklvsvariantofklothoisnotassociatedwithtype2diabetesin5028ukcaucasians AT hattersleya functionalklvsvariantofklothoisnotassociatedwithtype2diabetesin5028ukcaucasians AT fraylingt functionalklvsvariantofklothoisnotassociatedwithtype2diabetesin5028ukcaucasians |