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.


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.
Loew
Michael
M
Department of Epidemiology, German Centre for Research on Ageing at the University of Heidelberg, Heidelberg, Germany.
Hoffmann
Michael M
MM
Koenig
Wolfgang
W
Brenner
Hermann
H
Rothenbacher
Dietrich
D
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D055316:Cystatin C; D015891:Cystatins / Q000097:blood* / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies; D012307:Risk Factors
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins