Research Abstracts Online
January - December 2011
University of Minnesota Twin Cities
School of Public Health
Division of Epidemiology and Community Health
PI: Ajay Israni
Genomics of Kidney Transplantation
Long-term kidney allograft failure continues to be a major problem in the transplantation field. This group’s research results suggest that single nucleotide polymorphisms (SNPs) need to be studied along with detailed clinical risk factors for allograft outcomes such as acute rejection, chronic graft dysfunction and allograft failure. There do not appear to be any published genomics studies in kidney transplantation that have studied DNA genetic variants spanning the human genome.
This genome-wide association study (GWAS) will test the central hypothesis that common genetic variants in recipients and donors contributes to the observed variation in allograft function in recipients. The specific aims are to identify recipient and living donor SNPs from across the human genome that are associated with kidney allograft function. This prospective cohort study will use the existing 3,000 recipients and 1,000 living donors’ DNA samples already in the group’s DNA bank along with their clinical data. The clinical data is being collected in an existing database with high quality data. This database is linked with the United States Renal Data System, which reliably tracks all kidney transplant recipients in the United States. The SNPs associated with acute rejection, chronic allograft dysfunction and allograft failure will be validated in subsequently enrolled 3,000 recipient and 1,300 donor subjects. The researchers will also conduct meta-analyses with transplant recipients and their donors in external studies to validate these SNPs. The researchers hypothesize that these SNPs will help explain the impact of recipient and donor genetics on kidney allograft function. SNPs will be tested for association with kidney allograft function by Cox survival analysis. Exploratory analyses will also be conducted to investigate gene-gene interactions and gene-environment interactions. This study has the potential for meta-analysis with other genetic association studies to identify causal SNPs with modest effects. Study results will improve knowledge of genetic factors associated with allograft function, which in turn can suggest important mechanisms amenable to new prevention and treatment approaches.
John Holmes, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Jennifer Vigliaturo, Research Associate
Winston Wildebush, Research Associate