期刊
HUMAN HEREDITY
卷 66, 期 4, 页码 199-209出版社
KARGER
DOI: 10.1159/000143403
关键词
African-American; apo(a); kringle; Lp(a); plasminogen; sequencing; linkage disequilibrium
资金
- National Heart, Lung, and Blood Institute's Program for Genomic Applications [U01 HL66682, U01 HL66728]
- National Institute of Environmental Health Science's Environmental Genome Project [N01 ES15478]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [U01HL066728, U01HL066682] Funding Source: NIH RePORTER
Background/Aims: Lp(a) levels have long been recognized as a potential risk factor for coronary heart disease that is almost completely under genetic control. Much of the genetics impacting Lp(a) levels has been attributed to the highly polymorphic LPA kringle IV-2 copy number variant, and most of the variance in Lp(a) levels in populations of European-descent is inversely correlated with kringle IV copy number. However, less of the variance is explained in African-descent populations for the same structural variation. African-descent populations have, on average, higher levels of Lp(a), suggesting other genetic factors contribute to Lp(a) level variability across populations. Methods: To identify potential cis-acting factors, we resequenced the gene LPA for single nucleotide polymorphism (SNP) discovery in 23 European-Americans and 24 African-Americans. We also resequenced the neighboring gene plasminogen (PLG) and genotyped the kringle IV copy number variant in the same reference samples. Results: These data are the most comprehensive description of sequence variation in LPA and its relationship with the kringle IV copy number variant. With these data, we demonstrate that only a fraction of LPA sequence diversity has been previously documented. Also, we identify several high frequency SNPs present in the African-American sample but absent in the European-American sample. Finally, we show that SNPs within PLG are not in linkage disequilibrium with SNPs in LPA, and we show that kringle IV copy number variation is not in linkage disequilibrium with either LPA or PLG SNPs. Conclusions: Together, these data suggest that LPA SNPs could independently contribute to Lp(a) levels in the general population. Copyright (C) 2008 S. Karger AG, Basel.
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