In:
Geriatrics & Gerontology International, Wiley, Vol. 4, No. 2 ( 2004-06), p. 71-76
Kurzfassung:
Background: Plasma lipid and lipoprotein generally reflect the complex influences of multiple genetic loci, for instance, even familial hypercholesterolemia (FH), a representative example of monogenic hyperlipidemia, often presents with phenotypic heterogeneity. Methods: In the course of investigating familial coronary artery disease in Utah, we studied 160 members of an eight‐generation extended family of FH, to examine possible genetic modification of lipoprotein phenotype by ‘modifier locus’. G‐substrate (GSBS) is an endogenous substrate for cGMP‐dependent protein kinase. We carried out an intrafamilial correlation analysis of modifier effect of −1323T 〉 C substitution in the GSBS gene among 85 LDLR‐mutation carriers and 75 non‐carriers. Results: In the LDLR ‐ mutation carriers, the plasma cholesterol levels were highest among −1323C homozygotes (mean ± SD = 454 ± 101 mg/dL), lowest among −1323T homozygotes (mean ± SD, 307 ± 72 mg/dL) and intermediate among −1323T/C heterozygotes (mean ± SD, 314 ± 62 mg/dL; P = 0.015). Similarly, in the LDLR‐mutation carriers, the plasma triglyceride levels were highest among −1323C homozygotes (mean ± SD, 371 ± 381 mg/dL), lowest among −323T homozygotes (mean ± SD, 171 ± 94 mg/dL), and intermediate among −1323T/C heterozygotes (mean ± SD, 218 ± 130 mg/dL; P = 0.003). No such gene‐interactive effect was observed among non‐carriers of the LDLR‐mutation. Conclusion: These results indicate a significant modification of the phenotype of FH with defective LDLR allele, by GSBS‐1323C allele in the kindred studied.
Materialart:
Online-Ressource
ISSN:
1444-1586
,
1447-0594
DOI:
10.1111/ggi.2004.4.issue-2
DOI:
10.1111/j.1447-0594.2004.00126.x
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2004
ZDB Id:
2078308-5
