Journal of Lipid Research, Vol 32, 1513-1519, Copyright © 1991 by Lipid Research, Inc.

ARTICLES

Diverse effect of ethnicity on plasma lipoprotein[a] levels in heterozygote patients with familial hypercholesterolemia

E Leitersdorf, Y Friedlander, JM Bard, JC Fruchart, S Eisenberg and Y Stein
Department of Medicine B, Hadassah University Hospital, Jerusalem, Israel.

Plasma lipids, lipoproteins, and lipoprotein[a] (Lp[a]) levels were determined in 216 members of 14 families with familial hypercholesterolemia (FH). Ninety-nine subjects harbored a mutant low density lipoprotein (LDL) receptor allele as confirmed by molecular genetic analysis. Four different mutant alleles were identified, each in a defined genetic group, Druze, Christian-Arabs, and Ashkenazi and Sephardic Jews. The findings in FH subjects (cases) were compared with their nonaffected family members (controls). Plasma Lp[a] levels increased with age in the controls but not in cases and were different among the four genetic groups. Mean plasma Lp[a] levels were significantly higher in cases (33 mg/dl) than in controls (22 mg/dl). Plasma LDL cholesterol levels were raised in cases of the four genetic groups to a similar extent, in contrast to the mean plasma Lp[a] that varied. The Lp[a] level was higher by 30-33% in cases from the Druze, Christian-Arabs, and Jewish-Ashkenazi groups but by 110% in the Jewish- Sephardic group. Apo[a] isoform distribution was similar in cases and controls within each genetic group. Lp[a] levels were highest in subjects with LpS1 isoform, in particular in cases from the Jewish- Sephardic group. These data indicate that the higher Lp[a] levels in FH heterozygotes cannot be attributed solely to lack of functional LDL receptor molecules but possibly reflect multiple gene interactions.
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