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PMID: 18612205 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

LPA and PLG sequence variation and kringle IV-2 copy number in two populations.

Human heredity ·Vol. 66 ·No. 4 ·2008-00-00 ·Pages 199-209

Crawford DC, Peng Z, Cheng JF, Boffelli D, Ahearn M, Nguyen D, Shaffer T, Yi Q, Livingston RJ, Rieder MJ, Nickerson DA

Abstract

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. To identify potential cis-acting factors, we re-sequenced the gene LPA for single nucleotide polymorphism (SNP) discovery in 23 European-Americans and 24 African-Americans. We also re- sequenced the neighboring gene plasminogen (PLG) and genotyped the kringle IV copy number variant in the same reference samples. 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. Together, these data suggest that LPA SNPs could independently contribute to Lp(a) levels in the general population.

MeSH Terms
African Americans/genetics Alleles Blacks/genetics Gene Dosage Gene Frequency Genetic Variation Humans Kringles/genetics Linkage Disequilibrium Lipoprotein(a)/genetics Molecular Sequence Data Plasminogen/genetics Polymorphism, Single Nucleotide Sequence Analysis, DNA Whites/genetics
Chemicals
Lipoprotein(a) Plasminogen
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Crawford Dana C
Department of Molecular Physiology and Biophysics, Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37232, USA. [email protected]
Peng Ze
Cheng Jan-Fang
Boffelli Dario
Ahearn Magdalena
Nguyen Dan
Shaffer Tristan
Yi Qian
Livingston Robert J
Rieder Mark J
Nickerson Deborah A
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Article Info
Journal
Human heredity
Abbr.
Hum Hered
ISSN
1423-0062
DOI
10.1159/000143403
Email
[email protected]
Published
2008-00-00
Epub
2008-00-09
Pages
199-209
Language
English
Region
Switzerland
NLM ID
0200525
PMCID
PMC2861532
Subset
IM
Grants
NIEHS NIH HHS · N01ES15478 · United States
NHLBI NIH HHS · U01 HL66728 · United States
NHLBI NIH HHS · U01 HL66682 · United States
NIEHS NIH HHS · N01 ES15478 · United States
NHLBI NIH HHS · U01 HL066682 · United States
Databases
GENBANK
AY192161, DQ452068
External Links
PubMed source DOI: 10.1159/000143403 PMC Full Text View journal details
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