Tens of millions of individuals worldwide, suffer from end-stage diseases and congenital conditions, for which the only treatment, is the transplantation. Over 600,000 transplants were performed in US over the last five decades, and the demand today is higher than ever. Unfortunately, the availability of donor organs has not kept pace with demand.
Major advancements in organ preservation and drugs to suppress immune system have advanced patient survival. But there are still major issues with the rejection of the transplanted organs and immunosuppression drugs. Fortunately, scientists in the field of human genomics are making significant breakthroughs. Genomic tools have unveiled thousands of discoveries of specific genes and polymorphisms in every major disease area, typically by combining similar studies across different study sites. Many of these genetic discoveries are leading to new drug targets, repositioning of existing drugs, interventional treatments and even cures.
In a typical unrelated transplantation, approximately 4 million to 10 million genetic variants are observed between the genomes of a donor and a recipient. And certain regions of the genome, such as the ‘HLA region’ and the ‘KIR region’ are known to impact transplant outcomes. But our knowledge in this field is still in its infancy. There are very few single transplant genomic studies with sufficient numbers of transplant subjects to discover these genetic signals. There is a clear and compelling need for combining well characterized studies to increase the statistical power to discover these new genetic regions. The International Genetics & Translational Research in Transplantation Network (iGeneTRAiN) has brought together the major transplant genetic studies. It now encompasses over 32,000 samples from over a dozen countries with approximately 800,000 million genetic variants scanned across the genomes of these individuals.
iGeneTRAIN is currently combining genetic data from these subjects with the aim of detecting genes and specific variants underpinning rejection. A number of the iGeneTRAIN studies are also working on markers from urine and blood to predict rejection weeks to months before it manifests clinically.