title: CCR5 deletion protects against inflammation-associated mortality in dialysis patients.
abstract: The CC-chemokine receptor 5 (CCR5) is a receptor for various proinflammatory chemokines, and a deletion variant of the CCR5 gene (CCR5 Delta 32) leads to deficiency of the receptor. We hypothesized that CCR5 Delta 32 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 <or= 10 mg/L (n = 225), those carrying the deletion allele with hsCRP <or= 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 CCR5 Delta 32 polymorphism attenuates the adverse effects of inflammation on overall and cardiovascular mortality in ESRD.
authors.affiliation: University Medical Center Groningen, Department of Internal Medicine, Hanzeplein 1, PO Box 30001, 9700 RB Groningen, The Netherlands. f.l.h.muntinghe@int.umcg.nl
authors.forename: Friso L H
authors.initials: FL
authors.lastname: Muntinghe
authors.forename: Marion
authors.initials: M
authors.lastname: Verduijn
authors.forename: Mike W
authors.initials: MW
authors.lastname: Zuurman
authors.forename: Diana C
authors.initials: DC
authors.lastname: Grootendorst
authors.forename: Juan Jesus
authors.initials: JJ
authors.lastname: Carrero
authors.forename: Abdul Rashid
authors.initials: AR
authors.lastname: Qureshi
authors.forename: Karin
authors.initials: K
authors.lastname: Luttropp
authors.forename: Louise
authors.initials: L
authors.lastname: Nordfors
authors.forename: Bengt
authors.initials: B
authors.lastname: Lindholm
authors.forename: Vincent
authors.initials: V
authors.lastname: Brandenburg
authors.forename: Martin
authors.initials: M
authors.lastname: Schalling
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
authors.forename: Elisabeth W
authors.initials: EW
authors.lastname: Boeschoten
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Krediet
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Friedo W
authors.initials: FW
authors.lastname: Dekker
mesh_terms: D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000150:complications / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000378:metabolism / Q000517:prevention & control*; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000208:ethnology / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D011110:Polymorphism, Genetic / Q000235:genetics; D011446:Prospective Studies; D019713:Receptors, CCR5 / Q000235:genetics* / Q000378:metabolism; D006435:Renal Dialysis; D013548:Sweden
chemical_list: D019713:Receptors, CCR5; D002097:C-Reactive Protein