The association of common genetic variants in the APOA5, LPL and GCK genes with longitudinal changes in metabolic and cardiovascular traits

Webster, R. J., Warrington, N. M., Weedon, M. N., Hattersley, A. T., McCaskie, P. A., Beilby, J. P., Palmer, L. J. and Frayling, T. M. (2009) The association of common genetic variants in the APOA5, LPL and GCK genes with longitudinal changes in metabolic and cardiovascular traits. Diabetologia, 52 1: 106-114. doi:10.1007/s00125-008-1175-9


Author Webster, R. J.
Warrington, N. M.
Weedon, M. N.
Hattersley, A. T.
McCaskie, P. A.
Beilby, J. P.
Palmer, L. J.
Frayling, T. M.
Title The association of common genetic variants in the APOA5, LPL and GCK genes with longitudinal changes in metabolic and cardiovascular traits
Journal name Diabetologia   Check publisher's open access policy
ISSN 0012-186X
1432-0428
Publication date 2009-01-01
Year available 2009
Sub-type Article (original research)
DOI 10.1007/s00125-008-1175-9
Volume 52
Issue 1
Start page 106
End page 114
Total pages 9
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Subject 2712 Endocrinology, Diabetes and Metabolism
2724 Internal Medicine
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.
Keyword Association
Lipoprotein
Longitudinal
Diabetes
Type 2 diabetes
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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Created: Wed, 11 Jun 2014, 02:31:48 EST by Kylie Hengst on behalf of UQ Diamantina Institute