CCR5 Deletion Protects Against Inflammation-Associated Mortality in Dialysis Patients
AUTOR(ES)
Muntinghe, Friso L.H.
FONTE
American Society of Nephrology
RESUMO
The CC-chemokine receptor 5 (CCR5) is a receptor for various proinflammatory chemokines, and a deletion variant of the CCR5 gene (CCR5Δ32) leads to deficiency of the receptor. We hypothesized that CCR5Δ32 modulates inflammation-driven mortality in patients with ESRD. We studied the interaction between CCR5 genotype and levels of high-sensitivity C-reactive protein (hsCRP) in 603 incident dialysis patients from the multicenter, prospective NEtherlands COoperative Study on the Adequacy of Dialysis (NECOSAD) cohort. CCR5 genotype and hsCRP levels were both available for 413 patients. During 5 yr of follow-up, 170 patients died; 87 from cardiovascular causes. Compared with the reference group of patients who had the wild-type CCR5 genotype and hsCRP ≤ 10 mg/L (n = 225), those carrying the deletion allele with hsCRP ≤ 10 mg/L (n = 55) had similar mortality, and those carrying the wild-type genotype with hsCRP > 10 mg/L (n = 108) had an increased risk for mortality (HR: 1.82; 95% CI: 1.29 to 2.58). However, those carrying the deletion allele with hsCRP > 10 mg/L (n = 25) had a mortality rate similar to the reference group; this seemingly protective effect of the CCR5 deletion was even more pronounced for cardiovascular mortality. We replicated these findings in an independent Swedish cohort of 302 ESRD patients. In conclusion, the CCR5Δ32 polymorphism attenuates the adverse effects of inflammation on overall and cardiovascular mortality in ESRD.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2709675Documentos Relacionados
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