title: The genetics of IgA nephropathy.
abstract: IgA nephropathy is the most common form of primary glomerulonephritis. Variations in clinical manifestations indicate that a diagnosis of IgA nephropathy encompasses multiple disease subsets that cannot be distinguished on the basis of renal pathology or clinical variables alone. Familial forms of the disease have been reported throughout the world, but are probably under-recognized because associated urinary abnormalities are often intermittent in affected family members. IgA nephropathy has complex determination, with different genes probably causing disease in different patient subgroups. Of the many pathogenic mechanisms reported, defects in IgA1 glycosylation that lead to formation of immune complexes have been consistently implicated. Here, we present the evidence for genetic contributions to the disease, review clinical patterns of familial disease, and summarize some of the most promising genetic studies conducted to date. Linkage-based approaches to the study of familial forms of the disease have identified significant or suggestive loci on chromosomes 6q22-23, 2q36, 4q26-31, 17q12-22 and 3p24-23, but no causal gene has yet been identified. Many interesting, but poorly replicated, genetic association studies have also been reported. We discuss recent developments in analytic tools that should enable genetic studies of sporadic forms of disease by the genome-wide association approach.
authors.affiliation: Department of Genetics, Yale University, New Haven, CT, USA.
authors.forename: Isabel
authors.initials: I
authors.lastname: Beerman
authors.forename: Jan
authors.initials: J
authors.lastname: Novak
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wyatt
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Julian
authors.forename: Ali G
authors.initials: AG
authors.lastname: Gharavi
mesh_terms: D008040:Genetic Linkage / Q000235:genetics; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics; D040582:Inheritance Patterns / Q000235:genetics; D010375:Pedigree
chemical_list: D007070:Immunoglobulin A