Genetic Variation in LPAL2, LPA, and PLG Predicts Plasma Lipoprotein(a) Level and Carotid Artery Disease Risk

Overview

Journal Stroke

Specialties Cardiology & Vascular Diseases
Neurology

Date 2010 Dec 4

PMID 21127300

Citations 24

Authors

James Ronald

Ramakrishnan Rajagopalan

Felecia Cerrato

Alex S Nord

Thomas Hatsukami

Ted Kohler

Santica Marcovina

Patrick Heagerty

Gail P Jarvik

Affiliations

Soon will be listed here.

Abstract

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 LPA gene region and CAAD risk remains unknown.

Methods: we genotyped single nucleotide polymorphisms (SNPs) in the LPAL2, LPA, and PLG regions in 530 individuals with severe CAAD and 770 controls and kringle IV type 2 (KIV2) repeat length in a subset of 90 individuals.

Results: 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 LPA region was eliminated.

Conclusions: LPA region SNPs capture some but not all of the effect of KIV2 repeat length on Lp(a) level. There are associations between LPA region SNPs and CAAD that appear to be attributable to effects on Lp(a) level.

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