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A Simple Genetic Test For Kidney Disease

Background:
The National Cancer Institute's Laboratory of Genomic Diversity is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize genetic testing for kidney disease.

Technology:
An estimated 13% of the USA population has chronic kidney disease.The increased burden of chronic kidney disease (CKD) and end-stage kidney diseases (ESKD)  in populations of African ancestry has been largely unexplained.  The second and third leading causes of end stage renal disease are due to hypertension and glomerulopathies, mainly due to focal segmental glomerulosclerosis (FSGS) and HIV infection. ESRD is 4-fold higher in African Americans compared to their white counterparts.  Variations in a gene known as non-muscle myosin IIA (MYH9) are associated 70-100% of the excess risk for hypertension-associated ESRD (OR=2.2), idiopathic FSGS (OR=6-7), and HIV-associated nephropathy (OR=7).  MYH9 risk alleles are the strongest and most frequent yet discovered for common diseases with risk allele and haplotype frequencies of 60% in African Americans and 4% in European Americans.

A simple genetic screening test for one or a few of the single nucleotide polymorphisms will determine whether and individual is at increased or decreased risk of these forms of kidney disease. These variants are indicative of genetic risk for FSGS, collapsing glomerulopathy, HIV-associated nephropathy, hypertensive kidney disease, sickle cell nephropathy, lupus nephropathy, and possibly other kidney diseases. Because the factors are very frequent, and their effect on the risk of kidney disease very strong, these tests will have extraordinarily high predictive power compared to existing commercial tests for genetic risk of other common diseases.

Further R&D Needed:

• Extend findings to other forms of kidney disease in order to increase commercialization of this discovery
• Re-sequencing the gene to identify the causal allele
• Perform functional assays to determine how the causal allele alters structure or expression
• Survey populations throughout the world to determine the global distribution of the risk of SNPs and haplotypes
• Determine whether success of kidney allografts is affected by MYH9 genotype of the kidney donor.