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
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Media type:
E-Article
Title:
The functional "KL-VS" variant of KLOTHO is not associated with type 2 diabetes in 5028 UK Caucasians
Contributor:
Freathy, Rachel M;
Weedon, Michael N;
Melzer, David;
Shields, Beverley;
Hitman, Graham A;
Walker, Mark;
McCarthy, Mark I;
Hattersley, Andrew T;
Frayling, Timothy M
imprint:
Springer Science and Business Media LLC, 2006
Description:
<jats:title>Abstract</jats:title>
<jats:sec>
<jats:title>Background</jats:title>
<jats:p>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 <jats:italic>KLOTHO</jats:italic> (<jats:italic>KL</jats:italic>) 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.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods</jats:title>
<jats:p>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.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results</jats:title>
<jats:p>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 <jats:italic>P</jats:italic> > 0.05). However, the HDL-cholesterol levels observed across the genotype groups showed a similar, but non-significant, pattern to previously reported data.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusion</jats:title>
<jats:p>This is the first large-scale study to examine the association between common functional variation in <jats:italic>KL</jats:italic> 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.</jats:p>
</jats:sec>