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Pharmacogenet Genomics. 2009 Feb;19(2):161-9. doi: 10.1097/FPC.0b013e32831e030e.

Pharmacogenetic association of the APOA1/C3/A4/A5 gene cluster and lipid responses to fenofibrate: the genetics of lipid-lowering drugs and diet network study.

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  • 1Departments of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Abstract

BACKGROUND:

The apolipoproteins (APOA1/C3/A4/A5) are key components in modulating lipoprotein metabolism. It is unknown whether variants at the APOA1/C3/A4/A5 gene cluster are associated with lipid response to pharmacologic intervention.

METHODS AND RESULTS:

Plasma triglycerides (TGs) and high-density lipoprotein (HDL) levels were measured in 861 Genetics of Lipid-Lowering Drugs and Diet Network study participants who underwent a 3-week fenofibrate trial. We examined 18 common single nucleotide polymorphisms (SNPs) spanning the APOA1/C3/A4/A5 genes to investigate the effects of variants at the gene cluster on lipid response to fenofibrate treatment. We found that the minor alleles of the SNPs rs3135506 (APOA5_S19W), rs5104 (APOA4_N147S), rs4520 (APOC3_G34G), and rs5128 (APOC3_3U386) were associated with enhanced TG response to fenofibrate treatment (P= 0.0004-0.018). The minor allele of SNP rs2854117 (APOC3_M482) was associated with reduced rather than enhanced TG response (P= 0.026). The SNP rs3135506 (APOA5_S19W) was associated with HDL response, with minor allele related to reduced HDL response to fenofibrate (P= 0.002). Association analyses on haplotype provided corroborative evidence to single SNP association analyses. The common haplotypes H2, H3, and H5 were significantly associated with reduced TG response to fenofibrate.

CONCLUSION:

The genetic variants at APOA1/C3/A4/A5 gene cluster may be useful markers to predict response of lipid-lowering therapy with fenofibrate. Further studies to replicate/confirm our findings are warranted.

PMID:
19057464
[PubMed - indexed for MEDLINE]
PMCID:
PMC2733171
Free PMC Article

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