Lipoprotein Lipase ( LPL ) Gene Variation and Progression of Carotid Artery Plaque

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Abstract
Background and Purpose— Coding single nucleotide polymorphisms (cSNPs) in the lipoprotein lipase ( LPL ) gene have been associated with lipoprotein phenotypes and vascular disease risk. We studied the association between LPL cSNPs and a novel noninvasive measure of disease, namely, cross-sectional carotid plaque area (CPA) on B-mode ultrasound. Methods— Four hundred fifty-two patients from an atherosclerosis prevention clinic had determinations of baseline and total CPA. Traditional atherosclerosis risk factors were recorded, and the LPL D9N, N291S, and S447X cSNPs were genotyped. Multiple regression analysis was used to identify determinants of CPA. Results— Minor allele frequencies for LPL D9N, N291S, and S447X were 2.8%, 0.9%, and 4.4%, respectively. There were no significant between-genotype differences in treated fasting lipids. The LPL D9N genotype was a significant predictor of both baseline CPA ( P =0.008) and plaque progression from baseline to 1 year later ( P =0.001). Heterozygotes for the N9 allele had higher mean baseline CPA and plaque progression than did LPL D9/D9 homozygotes. Conclusions— LPL D9N genotype may be a determinant of atherosclerosis as estimated by static baseline CPA and by progression of CPA.