Highlights
- •APOA5 variants predispose to higher TG concentrations and modulate lipoprotein subclass distributions.
- •The atherogenic profile is associated with increased subclinical atherosclerosis.
- •The associations are exacerbated in overweight or patients with large waist circumference (≥90 cm in men and ≥85 cm in women).
Abstract
Background
Triglycerides (TG) are the initiators of the metabolic changes leading to the atherogenic
dyslipidemia, which is a major inducer of atherosclerosis as a result of quantitative
and qualitative changes in lipoprotein subclass distributions. We hypothesized that
variation at the of APOA5 gene locus, encoding apoAV, a key regulator of TG levels, significantly affect lipoprotein
subclass distributions toward a more atherogenic pattern in both hyperTG patients
and dyslipemic patients.
Methods
We recruited four hundred and twenty-two subjects attending a Lipid Clinic, prior
to lipid-lowering treatment. We genotyped two APOA5 variants, rs662799 (-1131T>C) and rs3135506 (S19W). Circulating lipoproteins were
determined by nuclear magnetic resonance (NMR). Intima-media thickness (IMT) was evaluated
using B-mode ultrasound.
Results
Carriers of the rare alleles of rs662799 and rs3135506 compared to common allele homozygotes,
had a significantly proatherogenic profile of the VLDL and LDL subclasses, resulting
in increased concentrations of the proatherogenic subclasses, large VLDLs (+133%,
p < 0.001) and small LDLs (+34%, p = 0.014). Significant changes in smaller HDL (+71%,
p = 0.032), as well as an 18% decrease in large HDL (p = 0.046), were also been observed.
This atherogenic NMR subclass distribution was significantly associated with increased
carotid IMT.
The observed effects were significantly stronger in patients with a BMI ≥ 25 kg/m2 and in male and female patients with a waist circumference ≥90 cm or ≥85 cm, respectively.
Conclusion
In a dyslipemic population, genetic variants of APOA5 modulate lipoprotein subclass distributions, inducing an atherogenic profile associated
with IMT defined subclinical atherosclerosis.
Keywords
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Article info
Publication history
Published online: March 10, 2015
Accepted:
March 3,
2015
Received in revised form:
February 24,
2015
Received:
November 20,
2014
Identification
Copyright
© 2015 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
