Abstract
Elevation in plasma triglycerides (TG) has been widely accepted as a coronary artery
disease (CAD) risk predictor. Recently, a new apolipoprotein playing an important
role in TG metabolism named apolipoprotein AV (apoAV) was discovered, which is encoded
by the APOA5 gene. Several single nucleotide polymorphisms (SNPs) of APOA5 associated with increased TG concentrations have been identified. We here report
that a recently identified genetic variant, c.553G > T in the APOA5 gene which causes a substitution of a cysteine for a glycine residue at amino acid
residue 185(G185C) is also associated with increased TG levels. To investigate the
association between this genetic variation and the risk of CAD, a case-control study
comprising 232 patients with CAD and 302 controls from the same area of China was
performed. The minor allele frequencies of c.553G > T for the CAD and control groups were 7.76 and 3.97%, respectively (P = 0.008). In both the CAD and control groups, the T allele carriers had higher serum
TG levels than homozygous carriers of the major G allele (CAD group: 2.67 ± 1.48 mmol/l versus 1.95 ± 1.02 mmol/l, P = 0.021; controls: 2.31 ± 1.20 mmol/l versus 1.68 ± 0.95 mmol/l, P = 0.002). After adjustment for age, gender, body mass index, smoking status, glucose
and presence of hypertension, the odds ratio (OR) for CAD in the T allele carriers
was 2.089 (95% CI = 1.140–3.830, P = 0.017), in comparison to the individuals without the T allele. These results suggest
that the APOA5 c.553G > T polymorphism is an important predictor for hypertriglyceridemia and CAD.
Keywords
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References
- Hypertriglyceridemia and elevated lipoprotein(a) are risk factors for major coronary events in middle-aged men.Am J Cardiol. 1996; 77: 1179-1184
- Hypertriglyceridemia as a cardiovascular risk factor.Am J Cardiol. 1998; 81: 7B-12B
- A risk factor for atherosclerosis: triglyceride-rich lipoproteins.Adv Intern Med. 2001; 47: 111-136
- Triglycerides: risk factor or fellow traveler?.Curr Opin Cardiol. 2001; 16: 261-264
- Genetic and environmental effects on coronary heart disease risk factors in northern Norway. The cardiovascular disease study in Finnmark.Ann Hum Genet. 1994; 58: 369-379
- Associations of genotypes at theapolipoprotein AI/CIII/AIV, apolipoprotein B and lipoprotein lipase gene loci with coronary atherosclerosis and high density lipoprotein subclasses.Clin Genet. 1994; 46: 273-282
- Restriction fragment length polymorphisms of the apolipoprotein A-I, C-III, A-IV gene locus. Relationships with lipids, apolipoproteins, and premature coronary artery disease.Atherosclerosis. 1991; 87: 75-86
- The apoAI-CIII-AIV gene cluster.Atherosclerosis. 2001; 157: 1-11
- An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing.Science. 2001; 294: 169-173
- Apolipoprotein AV: a novel apolipoprotein associated with a nearly phase of liver regeneration.J Biol Chem. 2001; 276: 44512-44520
- Adenovirus overexpression of apolipoprotein A–V reduces serum levels of triglycerides and cholesterol in mice.Biochem Biophys Res Commun. 2002; 295: 1156-1159
- The genetic effect of the apoprotein AV gene on the serum triglyceride level in Japanese.Atherosclerosis. 2002; 165: 201-204
- Association found between the promoter region polymorphism in the apolipoprotein A–V gene and the serum triglyceride level in Japanese school children.Hum Genet. 2002; 111: 570-572
- The single nucleotidepolymorphism −1131T > C in the apolipoprotein A5 (APOA5) gene is associated with elevated triglycerides in patients with hyperlipidemia.J Mol Med. 2003; 81: 645-654
- APOA5 −1131T > C polymorphism is associated with triglyceride levels in Chinese men.Clin Genet. 2003; 63: 377-379
- The −1131T > C polymorphism in the apolipoprotein A5 gene is associated with postprandial hypertriacylglycerolemia; elevated small, dense LDL concentrations; and oxidative stress in nonobese Korean men.Am J Clin Nutr. 2004; 80: 832-840
- A novel genetic variant in the apolipoprotein A5 gene is associated with hypertriglyceridemia.Hum Mol Genet. 2003; 12: 2533-2539
- New variants in the apolipoprotein AV gene in individuals with extreme triglyceride levels.Physiol Res. 2004; 53: 225-228
- Plasma triglyceride levels is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies.J Cardiovasc Risk. 1996; 3: 213-219
- Triglyceride concentration and ischemic heart disease: an 8-year follow-up in the copenhagen male study.Circulation. 1998; 97: 1029-1036
- Contribution of APOA5 gene variants to serum triglyceride determination and to the response to both fat and glucose tolerance challenges.Biochim Biophys Acta. 2003; 1637: 217-225
- The apolipoprotein A5 locus is a strong determinant of serum triglyceride concentrations across ethnic groups in Singapore.J Lipid Res. 2003; 44: 2365-2373
- Genetic analysis of a polymorphism in the human apoA–V gene: effect on serum lipids.J Lipid Res. 2003; 44: 1167-1173
- Relative contribution of variation within the APO3/A4/A5 gene cluster in determining plasma triglycerides.Hum Mol Genet. 2002; 11: 3039-3046
- Apolipoprotein A5, a newly identified gene that affects plasma triglyceride levels in humans and mice.Arterioscler Thromb Vasc Biol. 2003; 23: 529-534
- Structure and interfacial properties of human apolipoprotein AV.J Biol Chem. 2003; 278: 34438-34444
- Polymorphism in the promoter region of the apolipoprotein A5 gene is associated with an increased susceptibility for coronary artery disease.Atherosclerosis. 2004; 173: 109-114
- A single nucleotide polymorphism −1131T > C in the apolipoprotein A5 gene is associated with an increased risk of coronary artery disease and alters triglyceride metabolism in Chinese.Mol Genet Metab. 2004; 83: 280-286
- APOA5 gene polymorphism modulates levels of triglyceride, HDL cholesterol and FERHDL but it is not a risk factor for coronary artery disease.Atherosclerosis. 2004; 176: 165-172
- Apolipoprotein AIV gene variant S347 is associated with increased risk of coronary heart disease and lower plasma apolipoprotein AIV levels.Circ Res. 2003; 92: 969-975
Article info
Publication history
Published online: July 27, 2005
Accepted:
June 21,
2005
Received in revised form:
June 6,
2005
Received:
February 2,
2005
Identification
Copyright
© 2005 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.