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

Ali G. Gharavi, Yan Yan, Francesco Scolari, F. Paolo Schena, Giovanni M. Frasca, Gian Marco Ghiggeri, Kerry Cooper, Antonio Amoroso, Battista Fabio Viola, Graziana Battini, Gianluca Caridi, Cristina Canova, Anita Farhi, Vairavan Subramanian, Carol Nelson-Williams, Sue Woodford, Bruce A. Julian, Robert J. Wyatt, Richard P. Lifton

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)354-357
Number of pages4
JournalNature Genetics
Volume26
Issue number3
DOIs
Publication statusPublished - 2000

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ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Gharavi, A. G., Yan, Y., Scolari, F., Schena, F. P., Frasca, G. M., Ghiggeri, G. M., Cooper, K., Amoroso, A., Viola, B. F., Battini, G., Caridi, G., Canova, C., Farhi, A., Subramanian, V., Nelson-Williams, C., Woodford, S., Julian, B. A., Wyatt, R. J., & Lifton, R. P. (2000). IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23. Nature Genetics, 26(3), 354-357. https://doi.org/10.1038/81677