title: Chemokine receptor polymorphism and risk of acute rejection in human renal transplantation.
abstract: Chemokines regulate the trafficking of leukocytes in immunity and inflammation and have been implicated in mouse models in acute cardiac and renal allograft rejection; however, their significance to human transplantation is not yet defined. The association of human chemokine receptor genetic variants, CCR5-Delta32, CCR5-59029-A/G, CCR2-V64I, CX3CR1-V249I, and CX3CR1-T280M, with outcome in 163 renal transplant recipients was examined here. Significant reductions were found in risk of acute renal transplant rejection in recipients who possessed the CCR2-64I allele (odds ratio [OR], 0.30; 95% confidence interval [CI], 0.12 to 0.78; P = 0.014) or who were homozygous for the 59029-A allele (OR, 0.37; 95% CI, 0.16 to 0.85; P = 0.016). There were no significant differences in the incidence of rejection among patients stratified as with or without CCR5-Delta32 or by the CX3CR1-V249I or CX3CR1-T280M genotypes. Adjustment for known risk factors for transplant rejection confirmed the univariate findings for possession of the CCR2-64I allele (OR, 0.20; P = 0.032) and homozygosity for the 59029-A allele (OR, 0.26; P = 0.027). It was concluded that the risk of acute rejection in renal transplantation is associated with genetic variation in the chemokine receptors CCR2 and CCR5.
authors.affiliation: *Renal Division, Brigham and Women's Hospital, Boston, Massachesetts; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Reza
authors.initials: R
authors.lastname: Abdi
authors.affiliation: *Renal Division, Brigham and Women's Hospital, Boston, Massachesetts; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Tran Thi Bich
authors.initials: TTB
authors.lastname: Huong
authors.affiliation: *Renal Division, Brigham and Women's Hospital, Boston, Massachesetts; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Sahagun-Ruiz
authors.affiliation: *Renal Division, Brigham and Women's Hospital, Boston, Massachesetts; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Murphy
authors.affiliation: *Renal Division, Brigham and Women's Hospital, Boston, Massachesetts; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Barry M
authors.initials: BM
authors.lastname: Brenner
authors.affiliation: *Renal Division, Brigham and Women's Hospital, Boston, Massachesetts; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Edgar L
authors.initials: EL
authors.lastname: Milford
authors.affiliation: *Renal Division, Brigham and Women's Hospital, Boston, Massachesetts; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: David H
authors.initials: DH
authors.lastname: McDermott
mesh_terms: D000208:Acute Disease; D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic / Q000502:physiology*; D011184:Postoperative Period; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics*
chemical_list: C515334:CCR2 protein, human; C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine