on April 28, 2005
Published online before print April 28, 2005, doi: 10.1161/01.ATV.0000168416.74206.62
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Submitted on November 18, 2004
Accepted on April 14, 2005
Genotype and Plasma Concentration of Cystatin C in Patients With Coronary Heart Disease and Risk for Secondary Cardiovascular Events
Michael Loew ;
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.
* To whom correspondence should be addressed. 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.
Key words: coronary heart disease • cystatin C • genotype • prognosis • prospective study
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