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https://hdl.handle.net/2440/88486
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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 1432-0428 |
Statement of Responsibility: | 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 |
Published version: | http://dx.doi.org/10.1007/s00125-008-1175-9 |
Appears in Collections: | Aurora harvest 2 Translational Health Science publications |
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