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Genomic Study Identifies Kidney Disease Loci in Type I Diabetes Patients

By LabMedica International staff writers
Posted on 30 Sep 2019
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Image: A photomicrograph showing two glomeruli in diabetic kidney disease: the acellular light purple areas within the capillary tufts are the destructive mesangial matrix deposits (Photo courtesy of Wikimedia Commons).
Image: A photomicrograph showing two glomeruli in diabetic kidney disease: the acellular light purple areas within the capillary tufts are the destructive mesangial matrix deposits (Photo courtesy of Wikimedia Commons).
A large genome-wide association study (GWAS) identified 16 genetic loci linked to the development of kidney disease by individuals with type I diabetes.

Although earlier studies have found that diabetic kidney disease has a heritable component, searches for the genetic determinants of this complication of diabetes have had limited success.

To identify genetic variants that predispose people to diabetic kidney disease, investigators at Harvard Medical School (Boston, MA, USA) and their colleagues performed genome-wide association analyses on samples from19,406 individuals of European descent with type I diabetes, with and without kidney disease.

Results revealed 16 genome-wide loci linked to significant risk of developing kidney disease. The variant with the strongest association was a common missense mutation (a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid) in the collagen type IV alpha 3 chain (COL4A3) gene, which encodes a major structural component of the glomerular basement membrane (GBM).

Mutations in COL4A3 have been implicated in heritable kidney disorders, including the progressive inherited nephropathy Alport syndrome.

“This study represents a substantial advance in the genetics of diabetic kidney disease, where previous studies had yielded few robust associations,” said senior author Dr. Jose C. Florez, professor of medicine at Harvard Medical School. “The 16 diabetic kidney disease-associated regions provide novel insights into the pathogenesis of diabetic kidney disease, identifying potential biological targets for prevention and treatment.”

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