科研之友
微信
新浪微博
Facebook
分享链接
摘要
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 (eGFR(cys)). 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 eGFR(cys) and serum creatinine-based eGFR (eGFR(cr)) and performed longitudinal analyses of the associations of eGFR(cys) with mortality and cardiovascular events following adjustment for rs13038305. Outcomes: We assessed reclassification by genotype-adjusted eGFR(cys) across CKD categories:, 45, 45-59, 60-89, and >= 90mL/min/1.73m(2). We compared mortality and CVD outcomes in those reclassified to a worse eGFR(cys) category with those unaffected. Results were combined using fixed-effect inverse-variance meta-analysis. Results: In 14,645 participants, each copy of the T allele of rs13038305 (frequency, 21%) was associated with a 6.4% lower cystatin C concentration, 5.5-mL/min/1.73m(2) higher eGFR(cys), and 36%[95% CI, 29%-41%] lower odds of CKD. Associations with CVD (HR, 1.17; 95% CI, 1.14-1.20) and mortality (HR, 1.22; 95% CI, 1.19-1.24) per 10-mL/min/1.73m(2) lower eGFR(cys) were similar with or without rs13038305 adjustment. 1,134 (7.7%) participants were reclassified to a worse CKD category following rs13038305 adjustment, and rates of CVD and mortality were higher in individuals who were reclassified. However, the overall net reclassification index was not significant for either outcome, at 0.009 (95% CI, 20.003 to 0.022) for mortality and 0.014 (95% CI, 0.0 to 0.028) for CVD. Limitations: rs13038305 explains only a small proportion of cystatin C variation. Conclusions: Statistical adjustment can correct a genetic bias in GFR estimates based on cystatin C in carriers of the T allele of rs13038305 and result in changes in disease classification. However, on a population level, the effects on overall reclassification of CKD status are modest. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use.
- 出版日期2014-1
