SIGN-IN

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

All || By Area || By Year

Title Comprehensive analysis of genomic variation in the LPA locus and its relationship to plasma lipoprotein(a) in South Asians, Chinese and European Caucasians
Authors/Editors* Lanktree MB, Anand SS, Yusuf S, Hegele RA
Where published* Circulation: Cardiovas Genet
How published* Journal
Year* 2010
Volume 1
Number 3
Pages 39-46
Publisher
Keywords
Link 20160194
Abstract
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. METHODS AND RESULTS: 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%). CONCLUSIONS: 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).
Go to Genetic Linkage Analysis
Back to page 23 of list