Genotype and plasma concentration of cystatin C in patients with coronary heart disease and risk for secondary cardiovascular events.

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.