Apolipoprotein B genetic variants modify the response to fenofibrate: A GOLDN study

Mary K. Wojczynski, Guimin Gao, Ingrid Borecki, Paul N. Hopkins, Laurence Parnell, Chao Qiang Lai, Jose M. Ordovas, B. Hong Chung, Donna K. Arnett

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Hypertriglyceridemia, defined as a triglyceride measurement > 150 mg/dl, occurs in up to 34% of adults. Fenofibrate is a commonly used drug to treat hypertriglyceridemia, but response to fenofibrate varies considerably among individuals. We sought to determine if genetic variation in apolipoprotein B (APOB), an essential core of triglyceride-rich lipoprotein formation, may account for some of the inter-individual differences observed in triglyceride (TG) response to fenofibrate treatment. Participants (N = 958) from the Genetics of Lipid Lowering Drugs and Diet Network study completed a three-week intervention with fenofibrate 160 mg/day. Associations of four APOB gene single nucleotide polymorphisms (SNP) (rs934197, rs693, rs676210, and rs1042031) were tested for association with the TG response to fenofibrate using a mixed growth curve model where the familial structure was modeled as a random effect and cardiovascular risk factors were included as covariates. Three of these four SNPs changed the amino acid sequence of APOB, and the fourth was in the promoter region. TG response to fenofibrate treatment was associated with one APOB SNP, rs676210 (Pro2739Leu), such that participants with the TT genotype of rs676210 had greater TG lowering than those with the CC genotype (additive model, P = 0.0017). We conclude the rs676210 variant may identify individuals who respond best to fenofibrate for TG reduction.

Original languageEnglish
Pages (from-to)3316-3323
Number of pages8
JournalJournal of Lipid Research
Volume51
Issue number11
DOIs
StatePublished - Nov 2010

Keywords

  • Fenofibrate
  • Genetics of lipid lowering drugs and diet network
  • Polymorphism
  • Triglycerides

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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