APOA5 variants predispose hyperlipidemic patients to atherogenic dyslipidemia and subclinical atherosclerosis

作者：Guardiola Montse; Cofan Montserrat; de Castro Oros Isabel; Cenarro Ana; Plana Nuria; Talmud Philippa J; Masana Lluis; Ros Emilio; Civeira Fernando; Ribalta Josep^*

来源：Atherosclerosis, 2015, 240(1): 98-104.

DOI：10.1016/j.atherosclerosis.2015.03.008

• APOA5
• Polymorphisms
• NMR
• IMT
• Atherogenic dyslipidemia

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/m(2) 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.

• 出版日期2015-5