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Is IgA Nephropathy (IgAN) a Familial or Sporadic Disease?

  • Ichiei NaritaEmail author
  • Yoshikatsu Kaneko
  • Yumi Itoh
  • Yuichi Sakamaki
  • Seitaro Iguchi
  • Suguru Yamamoto
  • Minako Wakasugi
  • Junichiro J. Kazama
  • Shin Goto
Chapter

Abstract

There have been several lines of evidences for familial aggregation of IgA nephropathy (IgAN), as well as mesangial deposition of IgA, suggesting that the susceptibility to this disease is genetically controlled. In our institute, family histories of hematuria, end-stage kidney disease, and glomerulonephritis are observed in about 10 % of cases with IgAN, even in those without any significant hereditary nephritis or kidney diseases. Recent large-scale genome-wide association studies (GWAS) of sporadic IgAN have identified multiple susceptibility loci, providing an insight into the genetic architecture of this disease, although each of their individual impact to the development of the disease is still not enough. It has been recognized that most of these loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. Further elucidation of the role of genetic variants underlying IgAN, and hologenetic views of gene variants and environmental factors, would be necessary to understand the precise pathogenic mechanism of IgAN in more detail.

Keywords

Familial IgAN GWAS Exome sequencing 

Notes

Acknowledgment

This work was partly supported by Grant-in-Aid for Scientific Research (B) to I. Narita and (C) to S. Goto from the Japan Society for the Promotion of Science and also by MEXT KAKENHI (221S0002).

References

  1. 1.
    Donadio JV, Grande JP. IgA nephropathy. N Engl J Med. 2002;347:738–48.CrossRefPubMedGoogle Scholar
  2. 2.
    Glassock RJ, Kurokawa K, Yoshida M, Sakai O, Okada M, Shigematsu H, et al. IgA nephropathy in Japan. Am J Nephrol. 1985;5:127–37.CrossRefPubMedGoogle Scholar
  3. 3.
    Sugiyama H, Yokoyama H, Sato H, Saito T, Kohda Y, Nishi S, et al. Japan Renal Biopsy Registry and Japan Kidney Disease Registry: Committee report for 2009 and 2010. Clin Exp Nephrol. 2013;17:155–73.CrossRefPubMedGoogle Scholar
  4. 4.
    D’Amico G. The commonest glomerulonephritis in the world: IgA nephropathy. Q J Med. 1987;64:709–27.PubMedGoogle Scholar
  5. 5.
    Levy M, Berger J. Worldwide perspective of IgA nephropathy. Am J Kidney Dis. 1988;12:340–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Wyatt RJ, Julian BA, Baehler RW, Stafford CC, McMorrow RG, Ferguson T, et al. Epidemiology of IgA nephropathy in central and eastern Kentucky for the period 1975 through 1994. Central Kentucky Region of the Southeastern United States IgA Nephropathy DATABANK Project. J Am Soc Nephrol. 1998;9:853–8.PubMedGoogle Scholar
  7. 7.
    Sehic AM, Gaber LW, Roy 3rd S, Miller PM, Kritchevsky SB, Wyatt RJ. Increased recognition of IgA nephropathy in African-American children. Pediatr Nephrol. 1997;11:435–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Kiryluk K, Li Y, Sanna-Cherchi S, Rohanizadegan M, Suzuki H, Eitner F, et al. Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis. PLoS Genet. 2012;8, e1002765.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Suzuki K, Honda K, Tanabe K, Toma H, Nihei H, Yamaguchi Y. Incidence of latent mesangial IgA deposition in renal allograft donors in Japan. Kidney Int. 2003;63:2286–94.CrossRefPubMedGoogle Scholar
  10. 10.
    Cosyns JP, Malaise J, Hanique G, Mourad M, Baldi A, Goebbels RM, et al. Lesions in donor kidneys: nature, incidence, and influence on graft function. Transpl Int. 1998;11:22–7.CrossRefPubMedGoogle Scholar
  11. 11.
    Rosenberg HG, Martinez PS, Vaccarezza AS, Martinez LV. Morphological findings in 70 kidneys of living donors for renal transplant. Pathol Res Pract. 1990;186:619–24.CrossRefPubMedGoogle Scholar
  12. 12.
    Waldherr R, Rambausek M, Duncker WD, Ritz E. Frequency of mesangial IgA deposits in a non-selected autopsy series. Nephrol Dial Transplant. 1989;4:943–6.PubMedGoogle Scholar
  13. 13.
    Beerman I, Novak J, Wyatt RJ, Julian BA, Gharavi AG. The genetics of IgA nephropathy. Nat Clin Pract Nephrol. 2007;3:325–38.CrossRefPubMedGoogle Scholar
  14. 14.
    Karnib HH, Sanna-Cherchi S, Zalloua PA, Medawar W, D’Agati VD, Lifton RP, et al. Characterization of a large Lebanese family segregating IgA nephropathy. Nephrol Dial Transpl. 2007;22:772–7.CrossRefGoogle Scholar
  15. 15.
    Rambausek M, Hartz G, Waldherr R, Andrassy K, Ritz E. Familial glomerulonephritis. Pediatr Nephrol. 1987;1:416–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Scolari F, Amoroso A, Savoldi S, Mazzola G, Prati E, Valzorio B, et al. Familial clustering of IgA nephropathy: further evidence in an Italian population. Am J Kidney Dis. 1999;33:857–65.CrossRefPubMedGoogle Scholar
  17. 17.
    Wakai K, Kawamura T, Matsuo S, Hotta N, Ohno Y. Risk factors for IgA nephropathy: a case-control study in Japan. Am J Kidney Dis. 1999;33:738–45.CrossRefPubMedGoogle Scholar
  18. 18.
    Miyagawa S, Dohi K, Hanatani M, Yamanaka F, Okuchi T, Sakamoto K, et al. Anaphylactoid purpura and familial IgA nephropathy. Am J Med. 1989;86:340–2.CrossRefPubMedGoogle Scholar
  19. 19.
    Frasca GM, Soverini L, Gharavi AG, Lifton RP, Canova C, Preda P, et al. Thin basement membrane disease in patients with familial IgA nephropathy. J Nephrol. 2004;17:778–85.PubMedGoogle Scholar
  20. 20.
    Suzuki S, Suzuki Y, Kobayashi Y, Harada T, Kawamura T, Yoshida H, et al. Insertion/deletion polymorphism in ACE gene is not associated with renal progression in Japanese patients with IgA nephropathy. Am J Kidney Dis. 2000;35:896–903.CrossRefPubMedGoogle Scholar
  21. 21.
    Schena FP, D’Altri C, Cerullo G, Manno C, Gesualdo L. ACE gene polymorphism and IgA nephropathy: an ethnically homogeneous study and a meta-analysis. Kidney Int. 2001;60:732–40.CrossRefPubMedGoogle Scholar
  22. 22.
    Goto S, Narita I, Saito N, Watanabe Y, Yamazaki H, Sakatsume M, et al. A(-20)C polymorphism of the angiotensinogen gene and progression of IgA nephropathy. Kidney Int. 2002;62:980–5.CrossRefPubMedGoogle Scholar
  23. 23.
    Narita I, Goto S, Saito N, Song J, Omori K, Kondo D, et al. Angiotensinogen gene variation and renoprotective efficacy of renin-angiotensin system blockade in IgA nephropathy. Kidney Int. 2003;64:1050–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Narita I, Goto S, Saito N, Song J, Ajiro J, Sato F, et al. Interaction between ACE and ADD1 gene polymorphisms in the progression of IgA nephropathy in Japanese patients. Hypertension. 2003;42:304–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Song J, Narita I, Goto S, Saito N, Omori K, Sato F, et al. Gender specific association of aldosterone synthase gene polymorphism with renal survival in patients with IgA nephropathy. J Med Genet. 2003;40:372–6.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Sato F, Narita I, Goto S, Kondo D, Saito N, Ajiro J, et al. Transforming growth factor-beta1 gene polymorphism modifies the histological and clinical manifestations in Japanese patients with IgA nephropathy. Tissue Antigens. 2004;64:35–42.CrossRefPubMedGoogle Scholar
  27. 27.
    Feehally J, Farrall M, Boland A, Gale DP, Gut I, Heath S, et al. HLA has strongest association with IgA nephropathy in genome-wide analysis. J Am Soc Nephrol. 2010;21:1791–7.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Gharavi AG, Kiryluk K, Choi M, Li Y, Hou P, Xie J, et al. Genome-wide association study identifies susceptibility loci for IgA nephropathy. Nat Genet. 2011;43:321–7.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Yu XQ, Li M, Zhang H, Low HQ, Wei X, Wang JQ, et al. A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy. Nat Genet. 2012;44:178–82.CrossRefGoogle Scholar
  30. 30.
    Kiryluk K, Li Y, Scolari F, Sanna-Cherchi S, Choi M, Verbitsky M, et al. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat Genet. 2014;46:1187–96.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Li M, Foo JN, Wang JQ, Low HQ, Tang XQ, Toh KY, et al. Identification of new susceptibility loci for IgA nephropathy in Han Chinese. Nat Commun. 2015;6:7270.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Gharavi AG, Moldoveanu Z, Wyatt RJ, Barker CV, Woodford SY, Lifton RP, et al. Aberrant IgA1 glycosylation is inherited in familial and sporadic IgA nephropathy. J Am Soc Nephrol. 2008;19:1008–14.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, et al. Finding the missing heritability of complex diseases. Nature. 2009;461:747–53.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Gharavi AG, Yan Y, Scolari F, Schena FP, Frasca GM, Ghiggeri GM, et al. IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23. Nat Genet. 2000;26:354–7.CrossRefPubMedGoogle Scholar
  35. 35.
    Bisceglia L, Cerullo G, Forabosco P, Torres DD, Scolari F, Di Perna M, et al. Genetic heterogeneity in Italian families with IgA nephropathy: suggestive linkage for two novel IgA nephropathy loci. Am J Human Genet. 2006;79:1130–4.CrossRefGoogle Scholar
  36. 36.
    Paterson AD, Liu XQ, Wang K, Magistroni R, Song X, Kappel J, et al. Genome-wide linkage scan of a large family with IgA nephropathy localizes a novel susceptibility locus to chromosome 2q36. J Am Soc Nephrol. 2007;18:2408–15.CrossRefPubMedGoogle Scholar
  37. 37.
    Milillo A, La Carpia F, Costanzi S, D’Urbano V, Martini M, Lanuti P, et al. A SPRY2 mutation leading to MAPK/ERK pathway inhibition is associated with an autosomal dominant form of IgA nephropathy. Eur J Hum Genet: EJHG. 2015Google Scholar
  38. 38.
    Liu R, Hu B, Li Q, Jing X, Zhong C, Chang Y et al. Novel genes and variants associated with IgA nephropathy by co-segregating with the disease phenotypes in 10 IgAN families. Gene 2015.Google Scholar

Copyright information

© Springer Japan 2016

Authors and Affiliations

  • Ichiei Narita
    • 1
    Email author
  • Yoshikatsu Kaneko
    • 1
  • Yumi Itoh
    • 1
  • Yuichi Sakamaki
    • 1
  • Seitaro Iguchi
    • 1
  • Suguru Yamamoto
    • 1
  • Minako Wakasugi
    • 1
  • Junichiro J. Kazama
    • 1
  • Shin Goto
    • 1
  1. 1.Division of Clinical Nephrology and RheumatologyNiigata University Graduate School of Medical and Dental SciencesNiigataJapan

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