Submitted on February 9, 2007
Revised on June 5, 2007
Accepted on May 6, 2007
Genetic analysis of fluvastatin response and dyslipidemia in renal transplant recipients
Jonathan B. Singer, Hallvard Holdaas, Alan G. Jardine, Bengt Fellstrøm, Ingrid Os, Georgina Bermann, and Joanne M. Meyer
Clinical Pharmacogenetics, Novatis Institutes for Biomedical Research, Cambridge, MA 02139
Corresponding Author: jonathan.singer{at}novartis.com
The ALERT clinical trial demonstrated the efficacy of fluvastatin in reducing cardiovascular disease in renal transplant recipients. The study included a voluntary pharmacogenetic component, enrolling 1404 patients, which allowed association testing of baseline measures and longitudinal analysis of the 707 fluvastatin-treated and 697 placebo-treated individuals. A candidate gene approach, examining 42 polymorphisms in 18 genes, was used to test for association between selected polymorphisms and major adverse cardiac events (MACE), graft failure, change in LDL and HDL cholesterol, and baseline LDL and HDL cholesterol. Reported associations between CETP and baseline HDL cholesterol were replicated, with four previously implicated SNPs significantly associated in males and one in females; tests of reported associations between CETP and cardiovascular disease yielded varying results. We found no evidence for genetic factors affecting fluvastatin response. Polymorphisms in HMGCR previously reported to affect the efficacy of pravastatin did not show a similar effect on the lowering of LDL cholesterol by fluvastatin.
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