Genetic analysis of fluvastatin response and dyslipidemia in renal transplant recipients.
The Assessment of Lescol in Renal Transplantation clinical trial demonstrated the efficacy of fluvastatin in reducing cardiovascular (CV) disease in renal transplant recipients. The study included a voluntary pharmacogenetic component, enrolling 1,404 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, graft failure, change in LDL and HDL cholesterol, and baseline LDL and HDL cholesterol. Reported associations between cholesteryl ester transfer protein (CETP) and baseline HDL cholesterol were replicated, with four previously implicated single nucleotide polymorphisms significantly associated in males and one in females; tests of reported associations between CETP and CV disease yielded varying results. We found no evidence for genetic factors affecting fluvastatin response. Polymorphisms in 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) previously reported to affect the efficacy of pravastatin did not show a similar effect on the reduction of LDL cholesterol by fluvastatin.
Singer
Jonathan B
JB
Clinical Pharmacogenetics, Novartis Institutes for Biomedical Research, Cambridge, MA, USA. jonathan.singer@novartis.com
Holdaas
Hallvard
H
Jardine
Alan G
AG
Fellstrøm
Bengt
B
Os
Ingrid
I
Bermann
Georgina
G
Meyer
Joanne M
JM
D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000517:prevention & control; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D007211:Indoles / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic
C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D000077340:Fluvastatin; D006903:Hydroxymethylglutaryl CoA Reductases