Variants in the APOA5 gene region and the response to combination therapy with statins and fenofibric acid in a randomized clinical trial of individuals with mixed dyslipidemia
Objective: Atherogenic dyslipidemia is highly associated with coronary heart disease and is characterized by elevated triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), and elevated low-density lipoprotein cholesterol (LDL-C). The combination of statins and fibrates is a common modality to treat individuals with atherogenic dyslipidemia. We sought to identify single nucleotide polymorphisms (SNPs) associated with HDL-C, TG, and apolipoprotein A1 (ApoA-I) response to combination therapy with statins and fenofibric acid (FA) in individuals with atherogenic dyslipidemia.
Methods: 2228 individuals with mixed dyslipidemia who were participating in a multicenter, randomized, double-blind, active-controlled study comparing FA alone, in combination with a statin, or statin alone for a 12-week period, were genotyped for 304 candidate SNPs. A multivariate linear regression analysis for percent change in HDL-C, ApoA-I and TG levels was performed.
Results: SNPs in the apolipoprotein (APO) A5-ZNF259 region rs3741298 (P = 1.8 × 10(-7)), rs964184 (P = 3.6 × 10(-6)), rs651821 (P = 4.5 × 10(-5)), and rs10750097 (P = 1 × 10(-4)), were significantly associated with HDL-C response to combination therapy with statins and FA, with a similar association identified for ApoA-I. A haplotype composed of the minor alleles of SNPs rs3741298, rs964184, and rs10750097, was associated with a positive response to statins and FA (P = 8.7 × 10(-7)) and had a frequency of 18% in the study population.
Conclusion: In a population with atherogenic dyslipidemia, common SNPs and haplotypes within the APOA5-ZNF259 region are highly associated with HDL-C and ApoA-I response to combination therapy with statins and FA.
Publication ( Name of Journal)
Virani, S. S.,
Jones, P. H.,
Leal, S. M.,
Ballantyne, C. M.
(2011). Variants in the APOA5 gene region and the response to combination therapy with statins and fenofibric acid in a randomized clinical trial of individuals with mixed dyslipidemia. Atherosclerosis, 219(2), 737-742.
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