APOA5 variants predispose hyperlipidemic patients to atherogenic dyslipidemia and subclinical atherosclerosis. Issue 1 (May 2015)

• Record Type: Journal Article
• Authors: Guardiola, Montse; Cofán, Montserrat; de Castro-Oros, Isabel; Cenarro, Ana; Plana, Núria; Talmud, Philippa J.; Masana, Lluís; Ros, Emilio; Civeira, Fernando; Ribalta, Josep
• Is Part Of: Atherosclerosis. Volume 240:Issue 1(2015)
• Page Start: 98
• Page End: 104
• Publication Date: 2015-05
• Subjects: Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2015.03.008
• Languages: English
• ISSNs: 0021-9150

Abstract

<abstract xml:lang="en" abstract-type="author" id="abs0010"> <title id="sectitle0010">Abstract</title> <sec> <title id="sectitle0015">Background</title> <p id="abspara0010">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 <italic>APOA5</italic> 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.</p> </sec> <sec> <title id="sectitle0020">Methods</title> <p id="abspara0015">We recruited four hundred and twenty-two subjects attending a Lipid Clinic, prior to lipid-lowering treatment. We genotyped two <italic>APOA5</italic> 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.</p> </sec> <sec> <title id="sectitle0025">Results</title> <p id="abspara0020">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.</p> <p id="abspara0025">The observed effects were significantly stronger in patients with a BMI ≥ 25 kg/m<sup>2</sup> and in male and female patients with a waist circumference ≥90 cm or ≥85 cm, respectively.</p> </sec> <sec> <title id="sectitle0030">Conclusion</title> <p id="abspara0030">In a dyslipemic population, genetic variants of <italic>APOA5</italic> modulate lipoprotein subclass distributions, inducing an atherogenic profile associated with IMT defined subclinical atherosclerosis.</p> </sec> </abstract>