Genetic Clue to Risk of Diabetic Kidney Disease Discovered

Diabetic kidney disease is a major complication of diabetes and the leading cause of end-stage renal disease requiring dialysis treatment or kidney transplantation, as well as increased mortality due to other causes such as cardiovascular disease. However, not all those with diabetes, even those with poor glucose control, develop kidney disease and a strong clustering of diagnoses within families supports a genetic component to the risk. At present, the genes and the mechanisms behind the disease remain poorly understood, and few therapies are in development. Previous genetic studies have had limited success in identifying the genes responsible. The Genetics of Nephropathy: an International consortium effort (called GENIE), has undertaken a broad based analysis of genome-wide association studies of T1D kidney disease in 6,691 individuals. The group found an association between two specific genetic abnormalities and end stage renal disease. These potentially represent new signals in the disease process of diabetic kidney disease. Lab studies in cell models suggest that one of the genes may contribute to structural damage within the kidney. However, these are still very limited findings and there is a need for new approaches in discovering the genetic basis of diabetic kidney disease.

Ramifications for Individuals with T1D:
Diabetic kidney disease is a serious complication of T1D for which there are limited treatment options. Discovery and confirmation of the pathways involved in disease development are vital in order to target new therapies for the disease. Genetic studies should help to identify these pathways and may also lead to new disease markers to allow identification of those individuals with T1D most at risk of kidney disease.

JDRF Involvement:
JDRF funded GoKIND – one of the collections used in this effort, but did not fund the GENIE consortium.

Investigators and Institutions:
The GENIE consortium includes multiple US and European institutions.

Sandholm N, Salem RM, McKnight AJ, Brennan EP, Forsblom C, Isakova T, McKay GJ, Williams WW, Sadlier DM, Mäkinen VP, Swan EJ, Palmer C, Boright AP, Ahlqvist E, Deshmukh HA, Keller BJ, Huang H, Ahola AJ, Fagerholm E, Gordin D, Harjutsalo V, He B, Heikkilä O, Hietala K, Kytö J, Lahermo P, Lehto M, Lithovius R, Osterholm AM, Parkkonen M, Pitkäniemi J, Rosengård-Bärlund M, Saraheimo M, Sarti C, Söderlund J, Soro-Paavonen A, Syreeni A, Thorn LM, Tikkanen H, Tolonen N, Tryggvason K, Tuomilehto J, Wadén J, Gill GV, Prior S, Guiducci C, Mirel DB, Taylor A, Hosseini SM; DCCT/EDIC Research Group, Parving HH, Rossing P, Tarnow L, Ladenvall C, Alhenc-Gelas F, Lefebvre P, Rigalleau V, Roussel R, Tregouet DA, Maestroni A, Maestroni S, Falhammar H, Gu T, Möllsten A, Cimponeriu D, Ioana M, Mota M, Mota E, Serafinceanu C, Stavarachi M, Hanson RL, Nelson RG, Kretzler M, Colhoun HM, Panduru NM, Gu HF, Brismar K, Zerbini G, Hadjadj S, Marre M, Groop L, Lajer M, Bull SB, Waggott D, Paterson AD, Savage DA, Bain SC, Martin F, Hirschhorn JN, Godson C, Florez JC, Groop PH, Maxwell AP. (2012) New susceptibility loci associated with kidney disease in T1D. PLoS Genet. 2012 Sep;8(9):e1002921. doi: 10.1371/journal.pgen.1002921. Epub 2012 Sep 20.