Diverse effect of ethnicity on plasma lipoprotein[a] levels in heterozygote patients with familial hypercholesterolemia.
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.
Leitersdorf
E
E
Department of Medicine B, Hadassah University Hospital, Jerusalem, Israel.
Friedlander
Y
Y
Bard
J M
JM
Fruchart
J C
JC
Eisenberg
S
S
Stein
Y
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000235:genetics*; D007223:Infant; D007557:Israel; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011973:Receptors, LDL / Q000235:genetics
D017270:Lipoprotein(a); D008074:Lipoproteins; D011973:Receptors, LDL; D004247:DNA