CCR5 deletion protects against inflammation-associated mortality in dialysis patients.
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.
Muntinghe
Friso L H
FL
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
Verduijn
Marion
M
Zuurman
Mike W
MW
Grootendorst
Diana C
DC
Carrero
Juan Jesus
JJ
Qureshi
Abdul Rashid
AR
Luttropp
Karin
K
Nordfors
Louise
L
Lindholm
Bengt
B
Brandenburg
Vincent
V
Schalling
Martin
M
Stenvinkel
Peter
P
Boeschoten
Elisabeth W
EW
Krediet
Raymond T
RT
Navis
Gerjan
G
Dekker
Friedo W
FW
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
D019713:Receptors, CCR5; D002097:C-Reactive Protein