Effect of fenofibrate therapy and ABCA1 polymorphisms on high-density lipoprotein subclasses in the Genetics of Lipid Lowering Drugs and Diet Network
- PMID: 20346718
- PMCID: PMC3598593
- DOI: 10.1016/j.ymgme.2010.03.001
Effect of fenofibrate therapy and ABCA1 polymorphisms on high-density lipoprotein subclasses in the Genetics of Lipid Lowering Drugs and Diet Network
Abstract
Background: Previous studies have shown that ATP-binding cassette transporter 1 (ABCA1) polymorphisms associated with increased ABCA1 expression result in increased small HDL (high-density lipoprotein) subclass particle concentration. This study examines the effect of treatment with fenofibrate, a drug known to bind peroxisome proliferator-activated receptor alpha (PPARalpha) which increases the expression of ABCA1 gene, on lipoprotein subclass profiles of individuals stratified by ABCA1 genotypes.
Methods: Participants of Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) were treated with fenofibrate over a three week period. We analyzed six ABCA1 polymorphisms in 287 GOLDN participants with triglyceride concentrations >or=150mg/dL and studied their associations with HDL subclass particle concentrations, as measured by nuclear magnetic resonance spectroscopy, before and after treatment.
Results: Fenofibrate treatment did not result in significant changes in small HDL subclass particle concentration. When changes in HDL subclasses were stratified by ABCA1 polymorphism genotypes, there were no statistically significant associations between ABCA1 genotypes and small HDL subclasses before fenofibrate treatment. However, after fenofibrate treatment the KK genotype of R1587K (mean 4.40micromol/L; p=0.004) and the RK genotype of R219K (mean 1.60micromol/L; p=0.02) polymorphisms were associated with significantly increased small HDL. The R1587KKK genotype (mean 4.80micromol/L; p=0.0002) and the R219K KK genotype (mean 2.50micromol/L; p=0.02) were also associated with increased HDL particle concentrations.
Conclusion: There is a synergistic effect between ABCA1 polymorphisms and fenofibrate. Thus, our study indirectly confirms the role of fenofibrate and genotype in increasing cholesterol efflux, as evidenced by increased small HDL particles.
Similar articles
-
HDL in Morbidity and Mortality: A 40+ Year Perspective.Clin Chem. 2021 Jan 8;67(1):19-23. doi: 10.1093/clinchem/hvaa148. Clin Chem. 2021. PMID: 33221872 Free PMC article. Review. No abstract available.
-
ATP-binding cassette transporter A1 (ABCA1) R219K (G1051A, rs2230806) polymorphism and serum high-density lipoprotein cholesterol levels in a large Japanese population: cross-sectional data from the Daiko Study.Endocr J. 2015;62(6):543-9. doi: 10.1507/endocrj.EJ14-0577. Epub 2015 Apr 15. Endocr J. 2015. PMID: 25877294
-
Associations of genetic variants in ATP-binding cassette A1 and cholesteryl ester transfer protein and differences in lipoprotein subclasses in the multi-ethnic study of atherosclerosis.Clin Chem. 2009 Mar;55(3):481-8. doi: 10.1373/clinchem.2008.107995. Epub 2009 Jan 8. Clin Chem. 2009. PMID: 19131637 Free PMC article.
-
Genotypic variation in ATP-binding cassette transporter-1 (ABCA1) as contributors to the high and low high-density lipoprotein-cholesterol (HDL-C) phenotype.Transl Res. 2007 Apr;149(4):205-10. doi: 10.1016/j.trsl.2006.11.007. Transl Res. 2007. PMID: 17383594
-
ATP-binding cassette transporter AI and its role in HDL formation.Curr Opin Lipidol. 2005 Feb;16(1):19-25. doi: 10.1097/00041433-200502000-00005. Curr Opin Lipidol. 2005. PMID: 15650559 Review.
Cited by
-
Fibrate pharmacogenomics: expanding past the genome.Pharmacogenomics. 2020 Mar;21(4):293-306. doi: 10.2217/pgs-2019-0140. Epub 2020 Mar 17. Pharmacogenomics. 2020. PMID: 32180510 Free PMC article.
-
Association of single nucleotide polymorphisms with dyslipidemia in antiretroviral exposed HIV patients in a Ghanaian population: A case-control study.PLoS One. 2020 Jan 13;15(1):e0227779. doi: 10.1371/journal.pone.0227779. eCollection 2020. PLoS One. 2020. PMID: 31929604 Free PMC article.
-
Naoxintong Retards Atherosclerosis by Inhibiting Foam Cell Formation Through Activating Pparα Pathway.Curr Mol Med. 2018;18(10):698-710. doi: 10.2174/1566524019666190207143207. Curr Mol Med. 2018. PMID: 30734676 Free PMC article.
-
DNA methylation as a marker of response in rheumatoid arthritis.Pharmacogenomics. 2017 Sep;18(14):1323-1332. doi: 10.2217/pgs-2016-0195. Epub 2017 Aug 24. Pharmacogenomics. 2017. PMID: 28836487 Review.
-
An epigenome-wide association study of inflammatory response to fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network.Pharmacogenomics. 2017 Sep;18(14):1333-1341. doi: 10.2217/pgs-2017-0037. Epub 2017 Aug 24. Pharmacogenomics. 2017. PMID: 28835163 Free PMC article.
References
-
- Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC. Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation. 1998;98:2088–2093. - PubMed
-
- Hossain MA, Tsujita M, Gonzalez FJ, Yokoyama S. Effects of fibrate drugs on expression of ABCA1 and HDL biogenesis in hepatocytes. J. Cardiovasc. Pharmacol. 2008;51:258–266. - PubMed
-
- Ruan XZ, Moorhead JF, Fernando R, Wheeler DC, Powis SH, Varghese Z. PPAR agonists protect mesangial cells from interleukin 1beta-induced intracellular lipid accumulation by activating the ABCA1 cholesterol efflux pathway. J. Am. Soc. Nephrol. 2003;14:593–600. - PubMed
-
- Arakawa R, Tamehiro N, Nishimaki-Mogami T, Ueda K, Yokoyama S. Fenofibric acid, an active form of fenofibrate, increases apolipoprotein A-I-mediated high-density lipoprotein biogenesis by enhancing transcription of ATP-binding cassette transporter A1 gene in a liver X receptor-dependent manner. Arterioscler. Thromb. Vasc. Biol. 2005;25:1193–1197. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Molecular Biology Databases