0000000000531062
AUTHOR
Maria Lajer
Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen
BACKGROUND: Although diabetic kidney disease demonstrates both familial clustering and single nucleotide polymorphism heritability, the specific genetic factors influencing risk remain largely unknown.METHODS: To identify genetic variants predisposing to diabetic kidney disease, we performed genome-wide association study (GWAS) analyses. Through collaboration with the Diabetes Nephropathy Collaborative Research Initiative, we assembled a large collection of type 1 diabetes cohorts with harmonized diabetic kidney disease phenotypes. We used a spectrum of ten diabetic kidney disease definitions based on albuminuria and renal function.RESULTS: Our GWAS meta-analysis included association result…
Genome-wide association study of diabetic kidney disease highlights biology involved in renal basement membrane collagen
Diabetic kidney disease (DKD) is a heritable but poorly understood complication of diabetes. To identify genetic variants predisposing to DKD, we performed genome-wide association analyses in 19,406 individuals with type 1 diabetes (T1D) using a spectrum of DKD definitions basedon albuminuria and renal function. We identified 16 genome-wide significant loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain(COL4A3)gene, which encodes a major structural component of the glomerular basement membrane (GBM) implicated in heritable nephropathies. The rs55703767 minor allele (Asp326Tyr) is protective against several definit…
Urinary adiponectin excretion rises with increasing albuminuria in type 1 diabetes
Urinary adiponectin (u-adiponectin) excretion has been suggested to reflect early glomerular damage. Inspired by this, we studied the levels of u-adiponectin in type 1 diabetic patients with different levels of urinary albumin excretion (UAE).U-adiponectin was analysed by ELISA in type 1 diabetic patients: Fifty-eight with normoalbuminuria (30mg albumin/24h), 43 with persistent microalbuminuria (30-300mg/24h) and 44 with persistent macroalbuminuria (300mg/24h). For comparison, a control group of 55 healthy individuals was included.U-adiponectin increased with increasing levels of UAE (p0.01). U-adiponectin median (interquartile range): Normoalbuminuria 0.38 (0.14-1.31), microalbuminuria 1.1…