J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M500359-JLR200 on February 22, 2006

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Journal of Lipid Research, Vol. 47, 982-989, May 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Apo[a] size and PNR explain African American-Caucasian differences in allele-specific apo[a] levels for small but not large apo[a]

Jill Rubin*, Han Jo Kim*, Thomas A. Pearson{dagger}, Steve Holleran§, Rajasekhar Ramakrishnan§ and Lars Berglund1,*,**,{dagger}{dagger}

* Department of Medicine, Columbia University, New York, NY
{dagger} Department of Community and Family Medicine, University of Rochester, Rochester, NY
§ Department of Pediatrics, Columbia University, New York, NY
** Department of Medicine, University of California Davis, Davis, CA
{dagger}{dagger} Department of Veterans Affairs Northern California Health Care System, Sacramento, CA

Published, JLR Papers in Press, February 22, 2006.

1 To whom correspondence should be addressed. e-mail: lars.berglund{at}ucdmc.ucdavis.edu

Apolipoprotein [a] (apo[a]) gene size is a major predictor of lipoprotein [a] level. To determine genetic predictors of allele-specific apo[a] levels beyond gene size, we evaluated the upstream C/T and pentanucleotide repeat (PNR) polymorphisms. We determined apo[a] sizes, allele-specific apo[a] levels, and C/T and PNR in 215 Caucasians and 139 African Americans. For Caucasians, apo[a] size affected allele-specific levels substantially greater in subjects with apo[a] < 24 K4; for African Americans, the size effect was smaller than in Caucasians, <24 K4, but did not decrease at higher repeats. In both groups, the level decreased with increasing size of the other allele. Controlling for apo[a] sizes, PNR decreased allele-specific apo[a] levels in Caucasians with increasing PNR > 8. In a multiple regression model, apo[a] allele size and size and expression of the other apo[a] allele (and PNR > 8 for Caucasians) significantly predicted allele-specific apo[a] levels. For a common PNR 8 allele, predicted values were similar in the two ethnicities for small size apo[a]. Allele-specific apo[a] levels were influenced by the other allele size and expression. Observed differences between Caucasians and African Americans in allele-specific apo[a] levels were explained for small apo[a] sizes by the other allele size and PNR; the ethnicity differences remain unexplained for larger sizes.

Supplementary key words lipoprotein [a] • African Americans • genotyping • polymorphism • apolipoprotein [a] • pentanucleotide repeat


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