Genetic variants identified that may predispose patients with diabetes to kidney disease
Researchers have identified 16 genetic variants in patients with type 1 diabetes that may increase their likelihood of subsequently developing kidney disease.
“The devastating diabetic complication of diabetic kidney disease (DKD) is the major cause of end-stage renal disease (ESRD) worldwide,” Rany Salem, PhD, MPH, of the University of California San Diego, and colleagues wrote. “Current treatment strategies at best slow the progression of DKD, and do not halt or reverse the disease. Although improved glycemic control influences the rate of diabetic complications, a large portion of the variation in DKD remains unexplained ... Though DKD demonstrates both familial clustering and single nucleotide polymorphism (SNP) heritability, the specific genetic factors influencing DKD risk remain largely unknown.”
To identify these genetic factors, researchers conducted a meta-analysis of genome-wide association studies that included 19,406 patients with type 1 diabetes. Patients were categorized based on whether they also had kidney disease.
Researchers connected 16 genome-wide loci to diabetic kidney disease, noting that, although four “are in or near genes with known or suggestive biology related to renal function/collagen, (COL4A3, BMP7, COLEC11 and DDR1) ... this is the first time that naturally occurring variation [in] these loci has been associated with DKD.” The most “significant” signal found was a protective missense variant in COL4A3. According to the researchers, mutations in COL4A3 are responsible for heritable nephropathies, including the progressive inherited nephropathy Alport syndrome.
“Diabetic complications are unquestionably driven by hyperglycemia and partially prevented by improved glycemic control in both [type 1 and type 2 diabetes] T1D and T2D, but there has been doubt over what contribution, if any, inherited factors contribute to disease risk,” they wrote. “In line with previous genetic studies, this study with a markedly expanded sample size identified several loci strongly associated with DKD risk. These findings suggest that larger studies, aided by novel analyses and including T2D, will continue to enhance our understanding of the complex pathogenesis of DKD, paving the way for molecularly targeted preventive or therapeutic interventions.” – by Melissa J. Webb
Disclosures: Salem reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.