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ABIN1 Dysfunction as a Genetic Basis for Lupus Nephritis

Title
ABIN1 Dysfunction as a Genetic Basis for Lupus Nephritis
Author
배상철
Keywords
Animals; DNA-Binding Proteins; genetics; physiology; Fluorescent Antibody Technique; Humans; Kidney; pathology; physiopathology; Lupus Nephritis; etiology; Mice; Inbred C57BL; Knockout; NF-kappa B, Polymorphism; Single Nucleotide
Issue Date
2013-11
Publisher
American Society of Nephrology.
Citation
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 24(11), p.1743-1754
Abstract
The genetic factors underlying the pathogenesis of lupus nephritis associated with systemic lupus erythematosus are largely unknown, although animal studies indicate that nuclear factor (NF)-B is involved. We reported previously that a knockin mouse expressing an inactive form of ABIN1 (ABIN1[D485N]) develops lupus-like autoimmune disease and demonstrates enhanced activation of NF-B and mitogen-activated protein kinases in immune cells after toll-like receptor stimulation. In the current study, we show that ABIN1[D485N] mice develop progressive GN similar to class III and IV lupus nephritis in humans. To investigate the clinical relevance of ABIN1 dysfunction, we genotyped five single-nucleotide polymorphisms in the gene encoding ABIN1, TNIP1, in samples from European-American, African American, Asian, Gullah, and Hispanic participants in the Large Lupus Association Study 2. Comparing cases of systemic lupus erythematosus with nephritis and cases of systemic lupus erythematosus without nephritis revealed strong associations with lupus nephritis at rs7708392 in European Americans and rs4958881 in African Americans. Comparing cases of systemic lupus erythematosus with nephritis and healthy controls revealed a stronger association at rs7708392 in European Americans but not at rs4958881 in African Americans. Our data suggest that variants in the TNIP1 gene are associated with the risk for lupus nephritis and could be mechanistically involved in disease development via aberrant regulation of NF-B and mitogen-activated protein kinase activity.
URI
http://jasn.asnjournals.org/content/24/11/1743http://hdl.handle.net/20.500.11754/55001
ISSN
1533-3450
DOI
10.1681/ASN.2013020148
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > ETC
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