Chemokine receptor polymorphism and risk of acute rejection in human renal transplantation.
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.
Abdi
Reza
R
*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.
Huong
Tran Thi Bich
TTB
*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.
Sahagun-Ruiz
Alfredo
A
*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.
Murphy
Philip M
PM
*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.
Brenner
Barry M
BM
*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.
Milford
Edgar L
EL
*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.
McDermott
David H
DH
*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.
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*
C515334:CCR2 protein, human; C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine