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Journal of Lipid Research, Vol. 44, 1301-1305, July 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

Lack of genetic linkage evidence for a trans-acting factor having a large effect on plasma lipoprotein[a] levels in African Americans

Ruth Ann Barkley^*, Andrew C. Brown, Craig L. Hanis^*, Sharon L. Kardia, Stephen T. Turner^** and Eric Boerwinkle^1,*

^* Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030
Department of Medicine, University of Mississippi, Jackson, MS 39216
Department of Epidemiology, University of Michigan, Ann Arbor, MI 48109
^** Department of Internal Medicine and Division of Hypertension, Mayo Clinic, Rochester, MN 55905

¹ To whom correspondence should be addressed. e-mail: eboerwinkle{at}sph.uth.tmc.edu

The distribution of plasma lipoprotein[a] (Lp[a]) concentrations, a risk factor for cardiovascular disease, varies greatly among racial groups, with African Americans having values that are shifted toward higher levels than those of whites. The underlying cause of this heterogeneity is unknown, but a role for "trans-acting" factors has been hypothesized. This study used genetic linkage analysis to localize genetic factors influencing Lp[a] levels in African Americans that were absent in other populations; linkage results were analyzed separately in non-Hispanic whites, Hispanic whites, and African Americans. As expected, all three samples showed highly significant linkage at the approximate location of the lysophosphatidic acid locus. The white populations also independently had regions of significant linkage on chromosome 19 (LOD 3.80) and suggestive linkage on chromosomes 12 (LOD 1.60), 14 (LOD 2.56), and 19 (LOD 2.52).

No linkage evidence was found to support the hypothesis of another single gene with large effects specifically segregating in African Americans that may account for their elevated Lp[a] levels.

Supplementary key words lysophosphatidic acid • linkage analysis • genetics • population genetics

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