Common hepatic lipase gene promoter variant determines clinical response to intensive lipid-lowering treatment.
Circulation
; 103(6): 792-8, 2001 Feb 13.
Article
en En
| MEDLINE
| ID: mdl-11171785
ABSTRACT
BACKGROUND:
The common -514 C-->T polymorphism in the promoter region of the hepatic lipase (HL) gene affects HL activity. The C allele is associated with higher HL activity, more dense and atherogenic LDL, and lower HDL(2) cholesterol. Intensive lipid-lowering therapy lowers HL activity, increases LDL and HDL buoyancy, and promotes coronary artery disease (CAD) regression. We tested the hypothesis that subjects with the CC genotype and a more atherogenic lipid profile experience the greatest CAD regression from these favorable effects. METHODS ANDRESULTS:
Forty-nine middle-aged men with dyslipidemia and established CAD who were undergoing intensive lipid-lowering therapy were studied. Change in coronary stenosis was assessed by quantitative angiography, HL polymorphism by polymerase chain reaction amplification, HL activity by (14)C-labeled substrate, and LDL buoyancy by density-gradient ultracentrifugation. The response to lipid-lowering therapy was significantly different among subjects with different HL promoter genotypes. Subjects with the CC genotype had the greatest decrease in HL activity (P<0.005 versus TC and TT by ANOVA) and the greatest improvement in LDL density (P<0.005) and HDL(2)-C (P<0.05) with therapy. These subjects had the greatest angiographic improvement, with 96% of them experiencing CAD regression, compared with 60% of TC and none of the TT patients (P<0.001).CONCLUSIONS:
-In middle-aged men with established CAD and dyslipidemia, the HL gene -514 C-->T polymorphism significantly predicts changes in coronary stenosis with lipid-lowering treatment that appear to involve an HL-associated effect on LDL metabolism. This study identifies a gene polymorphism that strongly influences the lipid and clinical response to lipid-lowering drugs.
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Base de datos:
MEDLINE
Asunto principal:
Enfermedad Coronaria
/
Hiperlipidemias
/
Lipasa
/
Hígado
/
Hipolipemiantes
Tipo de estudio:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
Idioma:
En
Revista:
Circulation
Año:
2001
Tipo del documento:
Article