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|Objective:||To investigate the associations of APOA5 polymorphisms with CHD in a Chinese population|
|Study design:||Case control study. Three single nucleotide polymorphisms (SNPs), i.e. rs2075291, rs662799 and rs651821, were selected to identify the association between APOA5 gene polymorphism and CHD.|
|Study population:||710 subjects (355 patients with CHD and 355 controls) from Jilin, northeast China, who were recruited from a cross-sectional study. Inclusion criteria for CHD subjects were 1) angiographically confirmed coronary artery disease with ≥50% occlusion of at least one major coronary artery; 2) a confirmed myocardial infarction (MI); and 3) no diagnosis of liver, thyroid, pituitary or renal disease or history of acute or chronic inflammatory disease.|
· Plasma lipids
· Risk for CHD, as define above, according to carriage of the specified APOA5 variants
|Methods:||The χ2 test and haplotype analysis were used to analyse the associations between carriage of the APOA5 SNPs and CHD. A mediation model, incorporating three multivariate linear regression models adjusted for age and gender, was used to investigate whether levels of triglycerides act as a mediator of the associations between APOA5 polymorphisms and coronary artery disease. The level of statistical significance was p <0.05.|
|Conclusion:||Based on these data, variants of the APOA5 gene are associated with CHD susceptibility and may modulate levels of plasma triglycerides among a Chinese population.|
Genetic insights into the regulation of triglyceride-rich lipoproteins has offered alternative therapeutic approaches. In over 15 years since its discovery, there is now accumulating evidence that APOA5 is an important determinant of plasma triglycerides.1 Loss-of-function APOA5 variants have been shown to be associated with reduced lipolysis, poor remnant clearance and concomitantly, hypertriglyceridaemia, and also increased the risk of CHD in some but not all studies.2-5
The current study adds to evidence that APOA5 variants are associated with CHD risk in a Chinese cohort. The study was unique in using a mediation model to investigate whether the plasma level of triglycerides mediated the association of these two variants, rs651821 and rs662799, with CHD risk. Despite the limitations of a case-control study design and smaller sample size, the results from mediation modelling implicate triglycerides in the CHD risk associated with APOA5 loss-of-function variants in this Chinese cohort, and thus, reinforce evidence for the atheroprotective role of apolipoprotein A5.
1. Pennacchio LA, Olivier M, Hubacek JA et al. An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science 2001;294:169–73.
2. Pennacchio LA, Olivier M, Hubacek JA et al. Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels. Hum Mol Genet 2002;11:3031–8.
3. Talmud PJ, Hawe E, Martin S, et al. Relative contribution of variation within the APOC3/A4/A5 gene cluster in determining plasma triglycerides. Hum Mol Genet 2002;11:3039–46.
4. Hubacek JA. Apolipoprotein A5 fifteen years anniversary: Lessons from genetic epidemiology. Gene 2016;592:193-9.
5. Lee KW, Ayyobi AF, Frohlich JJ et al. APOA5 gene polymorphism modulates levels of triglyceride, HDL cholesterol and FERHDL but is not a risk factor for coronary artery disease. Atherosclerosis 2004;176:165–72.
|Key words||apolipoprotein A5, coronary heart disease risk; triglycerides; genetic study; mediation analysis|