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Type: Journal article
Title: The association of common genetic variants in the APOA5, LPL and GCK genes with longitudinal changes in metabolic and cardiovascular traits
Author: Webster, R.
Warrington, N.
Weedon, M.
Hattersley, A.
McCaskie, P.
Beilby, J.
Palmer, L.
Frayling, T.
Citation: Diabetologia, 2009; 52(1):106-114
Publisher: Springer
Issue Date: 2009
ISSN: 0012-186X
Statement of
R. J. Webster, N. M. Warrington, M. N. Weedon, A. T. Hattersley, P. A. McCaskie, J. P. Beilby, L. J. Palmer, T. M. Frayling
Abstract: AIMS/HYPOTHESIS Common genetic variants influence plasma triacylglycerol, HDL-cholesterol (HDL-C) and glucose levels in cross-sectional studies. However, the longitudinal effects of these established variants have not been studied. Our aim was to examine the longitudinal associations of four such variants in the apolipoprotein A-V (APOA5), lipoprotein lipase (LPL), and glucokinase (GCK) genes with fasting glucose or lipid levels. METHODS The individuals analysed were participants in the Busselton Health Survey (n = 4,554). Cross-sectional analyses of family data used the total association test. Longitudinal association analyses of unrelated participant data (n = 2,864) used linear mixed-effects models. RESULTS The findings of cross-sectional association analyses replicated those of previous studies. We observed associations of the G and C alleles at the APOA5 single nucleotide polymorphisms (SNPs) rs662799 and rs3135506 with raised triacylglycerol levels (p = 0.0003 and p < 0.0001, respectively), the 447X allele at the LPL SNP rs328 with reduced triacylglycerol levels (p = 0.0004) and raised HDL-C levels (p = 0.0004), and the A allele of the GCK SNP rs1799884 with raised fasting glucose level (p = 0.015). Longitudinal association analyses showed that most of these associations did not change in the same individuals over an average follow-up time of 17.4 years, though there was some evidence that the association of the 447X allele of rs328 with raised HDL-C level significantly increased with age (p = 0.01), and that the association of the C allele of rs3135506 with raised triacylglycerol level significantly increased over time (p = 0.0007). CONCLUSIONS/INTERPRETATION The current study suggests that the effects of established gene variants on lipid and glucose traits do not tend to alter with age during adulthood or over time.
Keywords: APOA5; Association; GCK; Longitudinal; LPL; SNP; Type 2 diabetes
Rights: © Springer-Verlag 2008
DOI: 10.1007/s00125-008-1175-9
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