Published online before print April 28, 2005, doi: 10.1161/01.ATV.0000168416.74206.62
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© 2005 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Genotype and Plasma Concentration of Cystatin C in Patients With Coronary Heart Disease and Risk for Secondary Cardiovascular Events
From the Department of Epidemiology (M.L., H.B., D.R.), German Centre for Research on Ageing at the University of Heidelberg, Heidelberg; the Department of Medicine (M.M.H.), Division of Clinical Chemistry, Albert Ludwigs University, Freiburg; and the Department of Internal Medicine II–Cardiology (W.K.), University of Ulm Medical Center, Ulm, Germany.
Correspondence to Wolfgang Koenig, Department of Internal Medicine II–Cardiology University of Ulm Medical Center Robert-Koch Str. 8 D-89081 Ulm, Germany. E-mail wolfgang.koenig{at}medizin.uni-ulm.de
Objective— Cysteine proteases and their inhibitors such as cystatin C are assumed to play an important role in the pathogenesis of atherosclerosis and coronary heart disease (CHD). The aim of the study was to investigate the impact of cystatin C polymorphisms on cystatin C plasma levels and on prognosis of patients with CHD.
Methods and Results— Four polymorphisms in the promoter and exon 1 of the cystatin C gene (–82GC, –5GA, +4AC, and +148AG) and cystatin C plasma levels were determined in a cohort of 1013 patients with manifest CHD and aged 30 to 70 years participating in an in-hospital rehabilitation program. Patients were followed-up for a mean of 33.5 months and a combined end point (fatal and nonfatal cardiovascular disease [CVD] events) was used as the outcome variable. The major haplotype –82G/–5G/+4A was associated with cystatin C plasma levels with persons homozygous for the major haplotype having the highest levels (P=0.01). However, the haplotype was not associated with fatal and nonfatal cardiovascular events during the 3-year follow-up.
Conclusions— The major haplotype –82G/–5G/+4A of the cystatin C gene determines plasma levels of cystatin C with homozygous persons having the highest plasma levels, but there was no association with secondary CVD events in this study.
The major haplotype –82G/–5G/+4A of the cystatin C gene was found to be associated with plasma concentration of cystatin C but not with prognosis of patients with CHD.
Key Words: coronary heart disease • cystatin C • genotype • prognosis • prospective study
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