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J Am Soc Nephrol 13:754-758, 2002
© 2002 American Society of Nephrology

Chemokine Receptor Polymorphism and Risk of Acute Rejection in Human Renal Transplantation

Reza Abdi*, Tran Thi Bich Huong*, Alfredo Sahagun-Ruiz{dagger}, Philip M. Murphy{dagger}, Barry M. Brenner*, Edgar L. Milford* and David H. McDermott{dagger}

*Renal Division, Brigham and Women’s Hospital, Boston, Massachesetts; {dagger}Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.

Correspondence to: Dr. David H. McDermott, LHD, NIAID/NIH, Bldg. 10, Room 11N111, 9000 Rockville Pike, Bethesda, MD 20892-1886. Phone: 301-496-8483; Fax: 301-402-4369: E-mail: dmcdermott{at}niaid.nih.gov

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-{Delta}32, 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-{Delta}32 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.




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