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Association of caveolin-1 gene polymorphism with kidney transplant fibrosis and allograft failure
- Publication Year :
- 2016
-
Abstract
- CONTEXT: 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. DESIGN, SETTING, AND PATIENTS: 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. MAIN OUTCOME MEASURE: 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%). CONCLUSION: Among kidney transplant donors, the CAV1 rs4730751 SNP was significantly associated with allograft failure in 2 independent cohorts.
- Subjects :
- Adult
Male
medicine.medical_specialty
Genotype
medicine.medical_treatment
Caveolin 1
Kidney
Gastroenterology
Cohort Studies
Internal medicine
medicine
Humans
Transplantation, Homologous
Genetic Predisposition to Disease
Treatment Failure
Kidney transplantation
Polymorphism, Genetic
Proportional hazards model
business.industry
General Medicine
Middle Aged
medicine.disease
Fibrosis
Kidney Transplantation
Tissue Donors
Surgery
Transplantation
England
Cohort
Female
Hemodialysis
business
Kidney disease
Cohort study
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....e3c8cecbdb85ee2dc08b2846261a2767