Association of a Cystatin C Gene Variant With Cystatin C Levels, CKD, and Risk of Incident Cardiovascular Disease and Mortality

Background Carriers of the T allele of the single-nucleotide polymorphism rs13038305 tend to have lower cystatin C levels and higher cystatin C–based estimated glomerular filtration rate (eGFRcys ). Adjusting for this genetic effect on cystatin C concentrations may improve GFR estimation, reclassify cases of chronic kidney disease (CKD), and strengthen risk estimates for cardiovascular disease (CVD) and mortality. Study Design Observational. Setting & Population 4 population-based cohorts: Atherosclerosis Risk in Communities (ARIC), Cardiovascular Health (CHS), Framingham Heart (FHS), and Health, Aging, and Body Composition (Health ABC) studies. Predictors We estimated the association of rs13038305 with eGFRcys and serum creatinine–based eGFR (eGFRcr ) and performed longitudinal analyses of the associations of eGFRcys with mortality and cardiovascular events following adjustment for rs13038305. Outcomes We assessed reclassification by genotype-adjusted eGFRcys across CKD categories: