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

Nature Genetics volume 26, pages 354–357 (2000)Cite this 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 population3,4,5,6 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 failure6,7,8,9. Although not generally considered a hereditary disease, striking ethnic variation in prevalence1,2,3,4,5,6,10 and familial clustering11,12,13,14,15,16, along with subclinical renal abnormalities among relatives of IgAN cases9,14,15,16, 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.

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Figure 1: Pathology of IgAN.
Figure 2: IgAN kindreds.
Figure 3: Linkage of IgAN to 6q22–23.

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Acknowledgements

We thank the members of the kindreds for participation; J. Budzinack for database assistance; M. Kashgarian for review of renal pathology; K. Choate for technical assistance; and N. Risch for helpful discussions. A.G.G. was supported by National Institutes of Health training grant and a gift by H. Printz. R.P.L. is an investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA

    Ali G. Gharavi, Yan Yan, Anita Farhi, Vairavan Subramanian, Carol Nelson-Williams & Richard P. Lifton

  2. Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA

    Richard P. Lifton

  3. Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA

    Kerry Cooper & Richard P. Lifton

  4. Department of Medicine, Mount Sinai School of Medicine, New York, New York, USA

    Ali G. Gharavi

  5. Division and Chair of Nephrology, Spedali Civili, University of Brescia, Brescia, Italy

    Francesco Scolari & Battista Fabio Viola

  6. Institute of Nephrology, University of Bari, Polyclinic, Bari, Italy

    F. Paolo Schena

  7. Nephrology Division, Policlinico S. Orsola, Bologna, Italy

    Giovanni M. Frasca

  8. Laboratory and Department of Nephrology, Giannina Gaslini Institute, Genoa, Italy

    Gian Marco Ghiggeri & Gianluca Caridi

  9. Servizio di Genetica e Cattedra di Genetica, IRCCS Burlo Garofolo, Trieste, Italy

    Antonio Amoroso

  10. Dialysis Service, Denzenzano Hospital, Desenzano, Italy

    Graziana Battini

  11. Nephrology Department, St Orsola University Hospital, Bologna, Italy

    Cristina Canova

  12. Crippled Children's Research Foundation, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA

    Sue Woodford & Robert J. Wyatt

  13. Department of Medicine, University of Alabama at Birmingham, Alabama, USA

    Bruce A. Julian

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Correspondence to Richard P. Lifton.

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Gharavi, A., Yan, Y., Scolari, F. et al. IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22–23. Nat Genet 26, 354–357 (2000). https://doi.org/10.1038/81677

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