Association of Caveolin-1 Gene Polymorphism With Kidney Transplant Fibrosis and Allograft Failure

被引:68
|
作者
Moore, Jason [1 ]
McKnight, Amy Jayne [4 ]
Simmonds, Matthew J. [2 ]
Courtney, Aisling E. [4 ]
Hanvesakul, Rajesh [1 ]
Brand, Oliver J. [2 ]
Briggs, David [3 ]
Ball, Simon [1 ]
Cockwell, Paul [1 ]
Patterson, Christopher C. [4 ]
Maxwell, Alexander P. [4 ]
Gough, Stephen C. L. [2 ]
Borrows, Richard [1 ]
机构
[1] Univ Hosp Birmingham, Renal Inst Birmingham, Dept Nephrol & Transplantat, Birmingham, W Midlands, England
[2] Univ Birmingham, Inst Biomed Res, Sch Clin & Expt Med, Coll Med & Dent Sci, Birmingham, W Midlands, England
[3] Natl Blood Serv, Birmingham, W Midlands, England
[4] Queens Univ Belfast, Nephrol Res Grp, Belfast, Antrim, North Ireland
来源
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION | 2010年 / 303卷 / 13期
关键词
CELLS;
D O I
10.1001/jama.2010.356
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 followup, 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. JAMA. 2010;303(13):1282-1287
引用
收藏
页码:1282 / 1287
页数:6
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