CCR5 Deletion Protects Against Inflammation- Associated Mortality in Dialysis Patients

TitleCCR5 Deletion Protects Against Inflammation- Associated Mortality in Dialysis Patients
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Year2009
Estimated date2009-04-01
CategoryScientific Publication
PlatformNone
DescriptionThe CC-chemokine receptor 5 (CCR5) is a receptor for various proinflammatory chemokines, and a deletion variant of the CCR5 gene (CCR532) leads to deficiency of the receptor. We hypothesized that CCR532 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 CCR532 polymorphism attenuates the adverse effects of inflammation on overall and cardiovascular mortality in ESRD. J Am Soc Nephrol 20: 1641–1649, 2009. doi: 10.1681/ASN.2008040432
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