Abstract P103: Genome-Wide Study of Gene Variants Associated with Differential Event Reduction by Pravastatin Therapy

Abstract

BACKGROUND : Statin therapy reduces the risk of coronary heart disease (CHD); however, the variability in response to statin therapy is not well understood. We investigated the effect of genetic variation on the reduction of CHD events by pravastatin therapy. METHODS : We genotyped 682 CHD cases from CARE and 383 CHD cases from WOSCOPS, two randomized placebo-controlled studies of pravastatin using the Illumina OMNI1 bead array. Single nucleotide polymorphisms (SNPs) that were associated with differential CHD event reduction by pravastatin therapy were investigated in PROSPER, a randomized placebo-controlled study of pravastatin in the elderly. RESULTS : A combined case-only analysis of CARE and WOSCOPS identified 62 SNPs associated with differential event reduction by pravastatin therapy (P int <0.0001 for interaction between treatment and genotype in an additive model). We investigated 57 of these SNPs in PROSPER. In an analysis that included cases as well as non-cases of CARE, WOSCOPS, and PROSPER, we found that for an intronic SNP in DNAJC5B (rs13279522), CHD event reduction by pravastatin therapy according to genotype differed in all 3 studies: P int =0.001 in CARE, P int =0.01 in WOSCOPS, P int =0.002 in PROSPER, and P int =3X10 -7 in a combined analysis of CARE, WOSCOPS and PROSPER (Figure). CONCLUSIONS : We have identified a SNP that is associated with differential event reduction by pravastatin therapy in CARE, WOSCOPS, and PROSPER. This SNP merits investigation in additional randomized studies of pravastatin and other statins.