Genetic variation in the PPARA gene is associated with simvastatin-mediated cholesterol reduction in the Rotterdam Study.
| Autor: | de Keyser CE; Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000CA Rotterdam, The Netherlands., Becker ML, Uitterlinden AG, Hofman A, Lous JJ, Elens L, Visser LE, van Schaik RH, Stricker BH |
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| Jazyk: | angličtina |
| Zdroj: | Pharmacogenomics [Pharmacogenomics] 2013 Aug; Vol. 14 (11), pp. 1295-304. |
| DOI: | 10.2217/pgs.13.112 |
| Abstrakt: | Aim: Recently, minor alleles of two strongly linked polymorphisms in the PPARA gene, rs4253728 G>A and rs4823613 A>G, were related to decreased CYP3A4 expression and activity. We studied whether they were associated with the cholesterol-lowering effect of simvastatin. Materials & Methods: We identified 123 incident users with cholesterol measurements before and after starting statin therapy in a prospective population-based cohort study. Associations between PPARA polymorphisms and change in total and low-density lipoprotein (LDL)-cholesterol levels were analyzed using linear regression. Results: The minor G allele of the rs4823613 A>G polymorphism was associated with a 0.258 mmol/l (95% CI: -0.470 to -0.046) and a 0.294 mmol/l (95% CI: -0.495 to -0.093) larger reduction in total and LDL-cholesterol, respectively, after starting simvastatin therapy. Results were similar for the rs4253728 G>A polymorphism. Conclusion: The minor alleles of the PPARA rs4253728 and rs4823613 polymorphisms are associated with a better total and LDL-cholesterol-lowering response to simvastatin, possibly through influence on CYP3A4. |
| Databáze: | MEDLINE |
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