Genetic studies of IgA nephropathy: past, present, and future |
| |
Authors: | Krzysztof Kiryluk Bruce A Julian Robert J Wyatt Francesco Scolari Hong Zhang Jan Novak Ali G Gharavi |
| |
Institution: | 1. Department of Medicine, Division of Nephrology, College of Physicians and Surgeons, Columbia University, 1150 St. Nicholas Avenue, Russ Berrie Pavilion #413, New York, NY, 10032, USA 2. Departments of Microbiology and Medicine, University of Alabama at Birmingham, Birmingham, AL, USA 3. Division of Pediatric Nephrology, Department of Pediatrics, Children’s Foundation Research Center at the Le Bonheur Children’s Medical Center, University of Tennessee Health Sciences Center, Memphis, TN, USA 4. Division of Nephrology, Università e Spedali Civili, Brescia, Italy 5. Renal Division of First Hospital, Institute of Nephrology, Peking University, Beijing, China
|
| |
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: | |
本文献已被 SpringerLink 等数据库收录! |
|