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Pediatric Nephrology

, Volume 25, Issue 11, pp 2257–2268 | Cite as

Genetic studies of IgA nephropathy: past, present, and future

  • Krzysztof Kiryluk
  • Bruce A. Julian
  • Robert J. Wyatt
  • Francesco Scolari
  • Hong Zhang
  • Jan Novak
  • Ali G. Gharavi
Educational Review

Abstract

Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide and an important cause of kidney disease in young adults. Highly variable clinical presentation and outcome of IgAN suggest that this diagnosis may encompass multiple subsets of disease that are not distinguishable by currently available clinical tools. Marked differences in disease prevalence between individuals of European, Asian, and African ancestry suggest the existence of susceptibility genes that are present at variable frequencies in these populations. Familial forms of IgAN have also been reported throughout the world but are probably underrecognized because associated urinary abnormalities are often intermittent in affected family members. Of the many pathogenic mechanisms reported, defects in IgA1 glycosylation that lead to formation of immune complexes have been consistently demonstrated. Recent data indicates that these IgA1 glycosylation defects are inherited and constitute a heritable risk factor for IgAN. Because of the complex genetic architecture of IgAN, the efforts to map disease susceptibility genes have been difficult, and no causative mutations have yet been identified. Linkage-based approaches have been hindered by disease heterogeneity and lack of a reliable noninvasive diagnostic test for screening family members at risk of IgAN. Many candidate-gene association studies have been published, but most suffer from small sample size and methodological problems, and none of the results have been convincingly validated. New genomic approaches, including genome-wide association studies currently under way, offer promising tools for elucidating the genetic basis of IgAN.

Keywords

IgA nephropathy Genetics Hereditary disease IgA1 glycosylation Genome-wide association study 

Notes

Acknowledgements

Krzysztof Kiryluk is supported by the Daland Fellowship from the American Philosophical Society and Grant Number KL2 RR024157 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Bruce A. Julian, Robert J. Wyatt, Francesco Scolari, Jan Novak, and Ali G. Gharavi are supported by Grant Number DK082753 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The authors also acknowledge other grants from NIDDK supporting their research of IgAN: DK078244, DK080301, DK075868, DK071802, and DK077279. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official view of NCRR, NIDDK, or NIH.

Conflicts of Interest

None

Supplementary material

467_2010_1500_MOESM1_ESM.doc (3.6 mb)
Table 1S Index of published genetic association studies in IgA nephropathy sorted by publication year (data from 1994 to 09/01/2009) (DOC 3642 kb)

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Copyright information

© IPNA 2010

Authors and Affiliations

  • Krzysztof Kiryluk
    • 1
  • Bruce A. Julian
    • 2
  • Robert J. Wyatt
    • 3
  • Francesco Scolari
    • 4
  • Hong Zhang
    • 5
  • Jan Novak
    • 2
  • Ali G. Gharavi
    • 1
  1. 1.Department of Medicine, Division of Nephrology, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA
  2. 2.Departments of Microbiology and MedicineUniversity of Alabama at BirminghamBirminghamUSA
  3. 3.Division of Pediatric Nephrology, Department of Pediatrics, Children’s Foundation Research Center at the Le Bonheur Children’s Medical CenterUniversity of Tennessee Health Sciences CenterMemphisUSA
  4. 4.Division of NephrologyUniversità e Spedali CiviliBresciaItaly
  5. 5.Renal Division of First Hospital, Institute of NephrologyPeking UniversityBeijingChina

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