IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23

Academic Article

Abstract

  • End-stage renal disease (ESRD) is a major public health problem, affecting 1 in 1,000 individuals and with an annual death rate of 20% despite dialysis treatment1,2. IgA nephropathy (IgAN) is the most common form of glomerulonephritis, a principal cause of ESRD worldwide1,2; it affects up to 1.3% of the population3-6 and its pathogenesis is unknown. Kidneys of people with IgAN show deposits of IgA-containing immune complexes with proliferation of the glomerular mesangium (Fig. 1). Typical clinical features include onset before age 40 with haematuria and proteinuria (blood and protein in the urine), and episodes of gross haematuria following mucosal infections are common; 30% of patients develop progressive renal failure6-9. Although not generally considered a hereditary disease, striking ethnic variation in prevalence1-6,10 and familial clustering11-16, along with subclinical renal abnormalities among relatives of IgAN cases9,14-16, have suggested a heretofore undefined genetic component. By genome-wide analysis of linkage in 30 multiplex IgAN kindreds, we demonstrate linkage of IgAN to 6q22-23 under a dominant model of transmission with incomplete penetrance, with a lod score of 5.6 and 60% of kindreds linked. These findings for the first time indicate the existence of a locus with large effect on development of IgAN and identify the chromosomal location of this disease gene.
  • Authors

    Published In

  • Nature Genetics  Journal
  • Digital Object Identifier (doi)

    Author List

  • Gharavi AG; Yan Y; Scolari F; Schena FP; Frasca GM; Ghiggeri GM; Cooper K; Amoroso A; Viola BF; Battini G
  • Start Page

  • 354
  • End Page

  • 357
  • Volume

  • 26
  • Issue

  • 3