The association of common genetic variants in the APOA5, LPL and GCK genes with longitudinal changes in metabolic and cardiovascular traits.
OBJECTIVE
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
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.
Webster
R J
RJ
Centre for Genetic Epidemiology and Biostatistics, University of Western Australia, B Block, Queen Elizabeth II Medical Centre, Nedlands, WA 6009, Australia. bwebster@meddent.uwa.edu.au
Warrington
N M
NM
Weedon
M N
MN
Hattersley
A T
AT
McCaskie
P A
PA
Beilby
J P
JP
Palmer
L J
LJ
Frayling
T M
TM
D000293:Adolescent; D000328:Adult; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D001315:Australia; D001786:Blood Glucose / Q000032:analysis*; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D014644:Genetic Variation; D005941:Glucokinase / Q000235:genetics*; D006306:Health Surveys; D006801:Humans; D008055:Lipids / Q000097:blood*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008137:Longitudinal Studies; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D001786:Blood Glucose; D008055:Lipids; D014280:Triglycerides; D004247:DNA; D005941:Glucokinase; D008071:Lipoprotein Lipase