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- Title
G-substrate gene promoter SNP (−1323T>C) modifies plasma total cholesterol and triglyceride phenotype in familial hypercholesterolemia: Intra-familial association study in an eight-generation hyperlipidemic kindred.
- Authors
Nobe, Yukiko; Sato, Keiko; Emi, Mitsuru; Ezura, Yoichi; Fujita, Yuko; Takada, Daisuke; Ishigami, Tomoaki; Umemura, Satoshi; Xin, Yunpei; Wu, Lily L.; Larrinaga-Shum, Stacey; Stephenson, Susan H.; Hunt, Steven C.; Hopkins, Paul N.
- Abstract
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. 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. 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. These results indicate a significant modification of the phenotype of FH with defective LDLR allele, by GSBS-1323C allele in the kindred studied.
- Subjects
CHOLESTEROL; TRIGLYCERIDES; HYPERCHOLESTEREMIA; HYPERLIPIDEMIA; PROTEIN kinases
- Publication
Geriatrics & Gerontology International, 2004, Vol 4, Issue 2, p71
- ISSN
1444-1586
- Publication type
Article
- DOI
10.1111/j.1447-0594.2004.00126.x