Lack of association of rs3798220 with small apolipoprotein(a) isoforms and high lipoprotein(a) levels in East and Southeast Asians
| Autor: | Florian Kronenberg, Wulf Schiefenhoevel, Ahmad Reza Bandegi, Wance Firdaus, R. W. C. Pang, Mahmoud A. Khalifa, Rhena Delport, Finney S. Geethanjali, Abdel Halim Salem, Gerd Utermann, Jun Sasaki, Asma Noureen, Konrad Schmidt, Orawan Makemaharn, Arno Lingenhel, Kathrin Ertelthalner, Kalpana Luthra |
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| Rok vydání: | 2015 |
| Předmět: |
Genetic Markers
China Linkage disequilibrium Asia DNA Copy Number Variations Genotype India Single-nucleotide polymorphism Genome-wide association study Coronary Artery Disease Polymorphism Single Nucleotide Asian People Gene Frequency Humans Protein Isoforms Allele frequency Alleles Apolipoproteins A Phylogeny Genetics biology Haplotype Genetic Variation Lipoprotein(a) Electrophoresis Gel Pulsed-Field Minor allele frequency Haplotypes Africa biology.protein Cardiology and Cardiovascular Medicine Genome-Wide Association Study |
| Zdroj: | Atherosclerosis. 242:521-528 |
| ISSN: | 0021-9150 |
| DOI: | 10.1016/j.atherosclerosis.2015.07.015 |
| Popis: | Objective The variant allele of rs3798220 in the apolipoprotein(a) gene ( LPA ) is used to assess the risk for coronary artery disease (CAD) in Europeans, where it is associated with short alleles of the Kringle IV-2 (KIV-2) copy number variation (CNV) and high lipoprotein(a) (Lp(a)) concentrations. No association of rs3798220 with CAD was detected in a GWAS of East Asians. Our study investigated the association of rs3798220 with Lp(a) concentrations and KIV-2 CNV size in non-European populations to explain the missing association of the variant with CAD in Asians. Methods We screened three populations from Africa and seven from Asia by TaqMan Assay for rs3798220 and determined KIV-2 CNV sizes of LPA alleles by pulsed-field gel electrophoresis (PFGE). Additionally, CAD cases from India were analysed. To investigate the phylogenetic origin of rs3798220, 40 LPA alleles from Chinese individuals were separated by PFGE and haplotyped for further SNPs. Results The variant was not found in Africans. Allele frequencies in East and Southeast Asians ranged from 2.9% to 11.6%, and were very low (0.15%) in CAD cases and controls from India. The variant was neither associated with short KIV-2 CNV alleles nor elevated Lp(a) concentrations in Asians. Conclusion Our study shows that rs3798220 is no marker for short KIV-2 CNV alleles and high Lp(a) in East and Southeast Asians, although the haplotype background is shared with Europeans. It appears unlikely that this SNP confers atherogenic potential on its own. Furthermore, this SNP does not explain Lp(a) attributed risk for CAD in Asian Indians. |
| Databáze: | OpenAIRE |
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