Lack of genetic linkage evidence for a trans -acting factor having a large effect on plasma lipoprotein(a) levels in

The distribution of plasma lipoprotein(a) (Lp(a)) concentrations, a risk factor for cardiovascular disease, var- ies 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 lo- calize genetic factors influencing Lp(a) levels in African Americans that were absent in other populations; linkage re- sults were analyzed separately in non-Hispanic whites, His- panic whites, and African Americans. As expected, all three samples showed highly significant linkage at the approxi- mate location of the lysophosphatidic acid locus. The white populations also independently had regions of significant linkage on chromosome 19 (LOD 3.80) and suggestive link- age 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 spe- cifically segregating in African Americans that may account for their elevated Lp(a) levels. —Barkley, R. A., A. C. Brown, C. L. Hanis, S. L. Kardia, S. T. Turner, and E. Boerwinkle. Lack of genetic linkage evidence for a trans -acting factor having a large effect on plasma lipoprotein(a) levels in Afri- can Americans. J. Lipid Res. 2003. 44: 1301-1305.