The goal of Project 1 is to use a genetic approach to identify the genes and pathways responsible for the development of Immunoglobulin A nephropathy (IgAN). IgAN is the most common form of primary glomerulonephritis and a significant cause of renal failure worldwide. The primary etiology of this disorder is unknown and there is no effective treatment currently available. By a genome-wider analysis of linkage, we have shown that in 60% of families with IgAN the disease is linked to an interval on chromosome 6q22-23, now called IGAN1. This genetic interval is supported with a peak lod score of 5.6 and confines the location of the disease gene to a 6.5 cM region. We now propose to replicate our findings in a new set of pedigrees, and narrow the IGAN1 interval to permit identification of the underlying gene. This will be accomplished by meiotic mapping in 20 newly recruited kindreds with IgAN and by disequilibrium mapping using a dense set of single nucleotide polymorphisms in 150 patients with sporadic IgAN who will be recruited from the southeastern United States. We will then proceed to positionally clone the underlying gene. Secondly, we plan to research for additional IgAN loci and study the significance of IGAN1 and these other loci in the pathogenesis of a related disorder, Henoch Schonlein purpura. Finally, using the information gathered by Core A and Projects 2 and 3 of this Program Project, we will perform genotype-phenotype correlation studies to determine the role of allelic and locus heterogeneity on the development of IgAN of IgAN and its complications.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
1P01DK061525-01
Application #
6555233
Study Section
Special Emphasis Panel (ZDK1)
Project Start
2002-04-01
Project End
2007-03-31
Budget Start
Budget End
Support Year
1
Fiscal Year
2002
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Hastings, M Colleen; Bursac, Zoran; Julian, Bruce A et al. (2018) Life Expectancy for Patients From the Southeastern United States With IgA Nephropathy. Kidney Int Rep 3:99-104
Tamouza, Houda; Chemouny, Jonathan M; Raskova Kafkova, Leona et al. (2012) The IgA1 immune complex-mediated activation of the MAPK/ERK kinase pathway in mesangial cells is associated with glomerular damage in IgA nephropathy. Kidney Int 82:1284-96
Novak, Jan; Raskova Kafkova, Leona; Suzuki, Hitoshi et al. (2011) IgA1 immune complexes from pediatric patients with IgA nephropathy activate cultured human mesangial cells. Nephrol Dial Transplant 26:3451-7
Camilla, Roberta; Suzuki, Hitoshi; Daprà, Valentina et al. (2011) Oxidative stress and galactose-deficient IgA1 as markers of progression in IgA nephropathy. Clin J Am Soc Nephrol 6:1903-11
Gomes, Michelle M; Suzuki, Hitoshi; Brooks, Monica T et al. (2010) Recognition of galactose-deficient O-glycans in the hinge region of IgA1 by N-acetylgalactosamine-specific snail lectins: a comparative binding study. Biochemistry 49:5671-82
Good, David M; Zürbig, Petra; Argilés, Angel et al. (2010) Naturally occurring human urinary peptides for use in diagnosis of chronic kidney disease. Mol Cell Proteomics 9:2424-37
Lavigne, K A; Woodford, S Y; Barker, C V et al. (2010) Familial IgA nephropathy in southeastern Kentucky. Clin Nephrol 73:115-21
Hastings, M Colleen; Moldoveanu, Zina; Julian, Bruce A et al. (2010) Galactose-deficient IgA1 in African Americans with IgA nephropathy: serum levels and heritability. Clin J Am Soc Nephrol 5:2069-74
Suzuki, Hitoshi; Fan, Run; Zhang, Zhixin et al. (2009) Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity. J Clin Invest 119:1668-77
Mischak, Harald; Coon, Joshua J; Novak, Jan et al. (2009) Capillary electrophoresis-mass spectrometry as a powerful tool in biomarker discovery and clinical diagnosis: an update of recent developments. Mass Spectrom Rev 28:703-24

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