Genetic Variation in
Predicts Plasma Lipoprotein(a) Level and Carotid Artery Disease Risk
Background and Purpose—
Lipoprotein(a) [Lp(a)] level is an established risk factor for coronary artery disease and has been implicated in carotid artery disease (CAAD). The relationship between genetic variation in the
gene region and CAAD risk remains unknown.
We genotyped single nucleotide polymorphisms (SNPs) in the
regions in 530 individuals with severe CAAD and 770 controls and kringle IV type 2 (KIV2) repeat length in a subset of 90 individuals.
Nine SNPs collectively accounted for 30% of the variance in Lp(a) level. Six SNPs were associated with Lp(a) level after accounting for KIV2 copy number, and the dominant KIV2 allele combined with these markers explained 60% of the variance in Lp(a) level. Five SNPs, including rs10455872, which had an odds ratio of 2.1 per minor allele and haplotypes formed by rs10455872, rs6919346, and rs3123629, were significant predictors of CAAD. After accounting for Lp(a) level, all evidence of CAAD–genotype association in the
region was eliminated.
region SNPs capture some but not all of the effect of KIV2 repeat length on Lp(a) level. There are associations between
region SNPs and CAAD that appear to be attributable to effects on Lp(a) level.
Ronald, J; Rajagopalan, R; Cerrato, F; Nord, AS; Hatsukami, T; Kohler, T; Marcovina, S; Heagerty, P; Jarvik, GP
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