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.
Highlights
Hypertriglyceridemia, defined as a triglyceride measurement > 150 mg/dl, occurs in up to 34% of adults
We examine the role of four polymorphisms in the apolipoprotein B (APOB) gene on the response of triglyceride levels to a three-week fenofibrate intervention of 160 mg/day of micronized fenofibrate among individuals participating in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study to further understand the variability in inter-individual response to fenofibrate treatment
Fenofibrate treatment reduces the production of APOB and secretion of very low-density lipoprotein (VLDL) [7, 30]
Summary
Hypertriglyceridemia, defined as a triglyceride measurement > 150 mg/dl, occurs in up to 34% of adults. 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. This article is available online at http://www.jlr.org acids, thereby reducing the amount of fatty acids available for TG synthesis [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
