Anton Van De Woestijne

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Rs964184 (APOA5-A4-C3-A1) is related to elevated plasma triglyceride levels, but not to an increased risk for vascular events in patients with clinically manifest vascular disease

A.P. van de Woestijne, Y. van der Graaf, P.I.W. de Bakker, F. W. Asselbergs, W. Spiering, F.L.J. Visseren for the SMART Study Group
Submitted

Abstract

Background: SNPs in the APOA5-A4-C3-A1 gene complex are associated with elevated plasma triglycerides (TG) and elevated vascular risk in healthy populations. In patients with clinically manifest vascular disease, hypertriglyceridemia and metabolic syndrome are frequently present, but the contribution of these SNPs to plasma TG, effect modification by obesity and risk of recurrent vascular events is unknown in these patients.

Methods: Prospective cohort study of 5547 patients with vascular disease. Rs964184 (APOA5-A4-C3-A1 gene complex) was genotyped, and we evaluated the relation with plasma lipid levels, presence of metabolic syndrome and the risk for new vascular events.

Results: Rs964184 was strongly associated with log plasma TG (ß 0.12; 95%CI 0.10-0.15, p=1.1*10-19), and was also associated with 0.03 mmol/L lower high-density lipoprotein-cholesterol (HDL-c) (95%CI 0.01-0.04), and 0.14 mmol/L higher nonHDL-c (95%CI 0.09-0.20). The minor allele frequency increased from 10.9% in patients with plasma TG <1 mmol/L to 24.6% in patients with plasma TG between 4 and 10 mmol/L. The relation between rs964184 and plasma TG was modified by body mass index (BMI) in patients with one minor allele (ß 0.02; (95%CI -0.04-0.09) if BMI <24 kg/m2, ß 0.17 (95%CI 0.12-0.22) if BMI >27 kg/m2, p for interaction=0.02). The prevalence of the metabolic syndrome increased from 52% for patients with two copies of the major allele to 62% for patients with two copies of the minor allele (p=0.01). Rs964184 was not related with recurrent vascular events (HR 0.99; 95%CI 0.86-1.13).

Conclusion: The SNP rs964184 (APOA5-A4-C3-A1) is associated with elevated plasma TG concentrations in patients with clinically manifest vascular disease. In carriers of one minor allele, the effect on plasma TG was modified by BMI. There is no relation between SNP rs964184 and recurrent vascular events in these patients.