Association of caveolin-1 gene polymorphism with kidney transplant fibrosis and allograft failure.
BACKGROUND
Caveolin-1 (CAV1) is an inhibitor of tissue fibrosis.


OBJECTIVE
To study the association of CAV1 gene variation with kidney transplant outcome, using kidney transplantation as a model of accelerated fibrosis.


METHODS
Candidate gene association and validation study. Genomic DNA from 785 white kidney transplant donors and their respective recipients (transplantations in Birmingham, England, between 1996 and 2006; median follow-up, 81 months) were analyzed for common variation in CAV1 using a single-nucleotide polymorphism (SNP) tagging approach. Validation of positive findings was sought in an independent kidney transplant donor-recipient cohort (transplantations in Belfast, Northern Ireland, between 1986 and 2005; n = 697; median follow-up, 69 months). Association between genotype and allograft failure was initially assessed by Kaplan-Meier analysis, then in an adjusted Cox model.


METHODS
Death-censored allograft failure, defined as a return to dialysis or retransplantation.


RESULTS
The presence of donor AA genotype for the CAV1 rs4730751 SNP was associated with increased risk of allograft failure in the Birmingham group (donor AA vs non-AA genotype in adjusted Cox model, hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.29-3.16; P = .002). No other tag SNPs showed a significant association. This finding was validated in the Belfast cohort (in adjusted Cox model, HR, 1.56; 95% CI, 1.07-2.27; P = .02). Overall graft failure rates were as follows: for the Birmingham cohort, donor genotype AA, 22 of 57 (38.6%); genotype CC, 96 of 431 (22.3%); and genotype AC, 66 of 297 (22.2%); and for the Belfast cohort, donor genotype AA, 32 of 48 (67%); genotype CC, 150 of 358 (42%); and genotype AC, 119 of 273 (44%).


CONCLUSIONS
Among kidney transplant donors, the CAV1 rs4730751 SNP was significantly associated with allograft failure in 2 independent cohorts.
Moore
Jason
J
Department of Nephrology and Transplantation, Renal Institute of Birmingham, University Hospital Birmingham, Birmingham B15 2TH, England.
McKnight
Amy Jayne
AJ
Simmonds
Matthew J
MJ
Courtney
Aisling E
AE
Hanvesakul
Rajesh
R
Brand
Oliver J
OJ
Briggs
David
D
Ball
Simon
S
Cockwell
Paul
P
Patterson
Christopher C
CC
Maxwell
Alexander P
AP
Gough
Stephen C L
SC
Borrows
Richard
R
D000328:Adult; D051242:Caveolin 1 / Q000235:genetics*; D015331:Cohort Studies; D004739:England; D005260:Female; D005355:Fibrosis; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014019:Tissue Donors; D014184:Transplantation, Homologous; D017211:Treatment Failure
D051242:Caveolin 1