Abstract P228: Genome-Wide Association Study of Lipid Response to Fenofibrate Treatment in the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) Study
The lipid-lowering drug fenofibrate (FF) is best known for its triglyceride (TG)-lowering properties, but it also reduces low-density lipoprotein (LDL), very low density lipoprotein (VLDL) and increases high-density lipoprotein concentrations (HDL). Response to FF varies considerably among individuals and may be under genetic influence. This study seeks to uncover genetic variants that underlie the interindividual response of TG, LDL, and VLDL to FF treatment.
Methods: TG, LDL, and VLDL concentrations were measured as part of the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) Study before and after a 3-week FF treatment (160 mg/day). Genotyping was done using the Affymetrix 6.0 genome-wide array. Lipid response phenotypes were generated using growth curve models adjusted for age, agê2, sex, and center. Associations between single nucleotide polymorphisms (SNPs) and lipid phenotypes were assessed with mixed linear models including kinship correlation structure using the R package LMEKIN .
Results: Genotype and TG, LDL, and VLDL response phenotype data were successfully collected from 769, 772, and 752 participants, respectively. The strongest evidence for association (P=3.80*10-7) was observed for LDL on chromosome 10 (133.7Mb) for SNP rs1646693. This lies near SLC35B4, a gene associated with obesity and glucose homeostasis. LDL also showed evidence of association (P=4.33*10-7) with rs6593376 on chromosome 10 (43.8Mb). The strongest evidence of association (P=5.54*10-7) with TG response was also on chromosome 10 (90.2Mb) at rs7917100 within RNLS, previously associated with cardiovascular function, cardiac hypertrophy, ischemia, and hypertension. Suggestive evidence of association (P=2.52*10-6) of rs11196872, with VLDL was also found on chromosome 10 (132Mb).
Conclusions: We identified several novel loci suggestively associated with TG, LDL, and VLDL response to fenofibrate treatment.
- © 2012 by American Heart Association, Inc.