Lipoprotein lipase locus and progression of atherosclerosis in coronary-artery bypass grafts

Abstract

Purpose: Our aim was to test whether polymorphisms in the lipoprotein lipase (LPL) gene were associated with the progression of atherosclerosis in grafts examined in the Post-Coronary Artery Bypass Graft Trial (Post-CABG Trial). Methods: 843 subjects in the post-CABG trial were genotyped for the LPL-D9N, N291S, Pvuli, (TTTA)n, and HindIII polymorphisms. Associations between genotype and angiographically measured progression of atherosclerosis in grafts, medical history, and family history were examined. Results: Greater progression of atherosclerosis was observed in subjects with LPL-HindIII 2/2 (56% versus 42% of those with other LPL HindIII genotypes, P = 0.025) and with LPL (TTTA)n 4/4 (63% versus 43% of those with other (TTTA)n genotypes, P = 0.020). Mantel-Haenszel analysis yielded an odds ratio of 1.84 for the effect of LPL HindIII 2/2 genotype on the progression of atherosclerosis in grafts (P = 0.015) and demonstrated that the effect of genotype on progression was of the same magnitude as, but independent of, the effect of drug treatment. Conclusion: The LPL-HindIII 2/2 genotype is a marker for genetic variation in the 3′-end of LPL that acts as an independent risk factor for the progression of atherosclerosis in grafts examined in the Post-CABG Trial.