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Circ Cardiovasc Genet. 2010 Feb;3(1):39-46. doi: 10.1161/CIRCGENETICS.109.907642. Epub 2009 Dec 30.

Comprehensive analysis of genomic variation in the LPA locus and its relationship to plasma lipoprotein(a) in South Asians, Chinese, and European Caucasians.

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  • 1Department of Medicine and Biochemistry, Robarts Research Institute and Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada.

Erratum in

  • Circ Cardiovasc Genet. 2011 Apr;4(2):e10.



Functional copy number variation in the apolipoprotein(a) gene (LPA) underlies a variable number of protein kringle domains repeated in tandem in the lipoprotein(a) [Lp(a)] particle. Genomic analysis of LPA, including both single-nucleotide polymorphisms (SNPs) and kringle IV type 2 (KIV-2) copy number, has yet to be performed.


First, we genotyped 49 SNPs within 100 kb of LPA in a multiethnic sample comprising South Asians (n=330), Chinese (n=304), and European Caucasians (n=272). Second, using quantitative polymerase chain reaction, we estimated the KIV-2 copy number in each sample. European Caucasians had the lowest KIV-2 copy number but displayed the strongest correlation between KIV-2 copy number and plasma Lp(a) concentration (r(s)=-0.31, P=4.2 x 10(-7)). SNP rs10455872, only prevalent in European Caucasians, was strongly associated with both plasma Lp(a) concentration (P=4.2 x 10(-29)) and KIV-2 copy number (P=7.2 x 10(-5)). LPA SNP rs6415084, within the same haplotype block as the KIV-2 variation, was significantly associated with both Lp(a) concentration and KIV-2 copy number in the same direction in all 3 ethnicities [Lp(a), P=5.3 x 10(-7); KIV-2, P=2.6 x 10(-4)]. SNPs and KIV-2 copy number together explain a larger proportion of variation in plasma Lp(a) concentrations in European Caucasians (36%) than in Chinese (27%) or South Asians (21%).


LPA SNPs are in linkage disequilibrium with KIV-2 copy number, but KIV-2 copy number explains an increment in plasma Lp(a) variation over SNPs alone. Thus, both SNPs and KIV-2 copy number should be included in future genetic epidemiology studies of Lp(a).

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