CHALLENGES IN ASSOCIATION STUDIES OF SINGLE NUCLEOTIDE POLYMORPHISM ASSOCIATED AND RENAL TRANSPLANT OUTCOMES
Ajay Israni, Assistant Professor of Medicine, Adjunct Professor of Epidemiology & Community Health, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN, USA
1. To understand issues of study design related to single nucleotide polymorphisms (SNPs) in transplantation.
2. To understand challenges of analyzing outcomes data in genetic epidemiology studies.
3. Consider the future direction for studies of genomic variation in transplantation.
The Genomics of Transplantation is a NIH funded genetic ancillary to an ongoing prospective cohort of renal transplant recipients. This ongoing, international, multi-center cohort is Deterioration of Kidney Allograft Function (DeKAF) study (PI, Arthur Matas). We will discuss the issues relevant to the design of our Genomics of Transplantation study. Our study includes 2 projects, genetic epidemiology project (Project Leader, Ajay Israni) and pharmacogenomics (Project Leader, Pamala Jacobson). All study subjects are prospectively enrolled, kidney transplant recipients and their living donors, at the 6 study sites of DeKAF. Target enrollment is 4,000 recipients in the test and validation cohorts. Sites are: University of Minnesota and Hennepin County Medical Center, Minneapolis, MN; University of Alberta, Edmonton, Canada; University of Iowa, Iowa City, IA; University of Alabama, Birmingham, AL; and the Mayo Clinic, Rochester, MN. Genotyping will employ a custom Affymetrix chip with 3,500 functional single nucleotide polymorphisms (SNPs) in the Genotyping Core (Core Leader, William Oetting).
The genetic epidemiology project will study the relationship SNPs of recipient and donor genes with chronic allograft dysfunction (CGD) and estimated glomerular filtration rate (eGFR). The project will also compare the frequency of SNPs that are associated with CGD and eGFR among African Americans (AA) and non-AA, given the increased risk of allograft loss among AA.
The pharmacogenomics project will test the hypothesis that SNPs of drug metabolizing enzymes, transporters, drug targets and biological pathways are associated with immunosuppressant exposure, adverse effects and clinical outcomes.
The results from the test cohort of both projects will be discussed.