Adhesion molecule polymorphisms in chronic renal allograft failure.
BACKGROUND
Chronic allograft failure (CAF) is a major cause of late graft loss in renal transplantation. Up-regulation of adhesion molecules has been demonstrated in renal allograft biopsies during both acute and chronic rejection, and these molecules are known to regulate leukocyte migration into the graft.


METHODS
A single-center retrospective study was performed between 1985 and 1996 on renal transplant recipients who developed CAF. Genotyping was performed for five polymorphisms in intercellular adhesion molecule-1 (ICAM-1), E-selectin, and L-selectin. Frequency data for the polymorphisms in the CAF group (N = 62) and their matched donors, where available (N = 33), were compared with a group of recipients with graft survival of more than 10 years (N = 110) and a group of United Kingdom (UK) controls (N = 101).


RESULTS
A variant allele in exon 4 of ICAM-1 (R241) was more common in the CAF recipients compared with both long-term survivors and UK controls (19.4 vs. 10.0 and 9.4%, P = 0.015 and 0.025). In addition, stratification by time to graft failure caused by CAF revealed more rapid failure in the presence of another ICAM-1 variant in the recipient (E469) in exon 6 (P = 0.033).


CONCLUSIONS
ICAM-1 polymorphisms may represent a predetermined genetic risk factor for CAF. The polymorphism in exon 4 is in the Mac-1 binding site, and that in exon 6 is in the fifth immunoglobulin-like domain. Potential mechanisms of action of ICAM-1 variants in CAF include an alteration of activity as an adhesion molecule, altered costimulation, or a minor histocompatibility antigen.
McLaren
A J
AJ
Nuffield Department of Surgery, John Radcliffe Hospital, Oxford, England, United Kingdom. Amcla007@aol.com
Marshall
S E
SE
Haldar
N A
NA
Mullighan
C G
CG
Fuggle
S V
SV
Morris
P J
PJ
Welsh
K I
KI
D000483:Alleles; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000235:genetics*; D019040:E-Selectin / Q000235:genetics; D006084:Graft Rejection / Q000235:genetics*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007668:Kidney / Q000098:blood supply / Q000737:chemistry / Q000601:surgery; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D016030:Kidney Transplantation; D019041:L-Selectin / Q000235:genetics; D007962:Leukocytes / Q000166:cytology; D011110:Polymorphism, Genetic; D012079:Renal Circulation / Q000502:physiology; D015427:Reperfusion Injury / Q000235:genetics; D012189:Retrospective Studies; D016019:Survival Analysis
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin