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ABIN1 Dysfunction as a Genetic Basis for Lupus Nephritis

Authors :
Carl D. Langefeld
Gary S. Gilkeson
John B. Harley
Ryan M. Sheehan
Chaim O. Jacob
Susan A. Boackle
Timothy B. Niewold
Anne M. Stevens
John D. Reveille
Betty P. Tsao
Jeffrey C. Edberg
Rachel T. G'Sell
Erik A. Korte
Barry I. Freedman
K R McLeish
Rebecca K. Oliver
Darrell W. Freeman
Judith A. James
Juan-Manuel Anaya
Diane L. Kamen
Marta E. Alarcón-Riquelme
Susan Coventry
Patrick M. Gaffney
Lindsey A. Criswell
Indra Adrianto
Rosalind Ramsey-Goldman
Sang Cheol Bae
Bernardo A. Pons-Estel
Dawn J. Caster
Jennifer A. Kelly
Michelle Petri
Sambit K. Nanda
Javier Martin
David W. Powell
Kenneth M. Kaufman
Joel M. Guthridge
Kathy L. Sivils
Robert P. Kimberly
Elizabeth E. Brown
Luis M. Vilá
Graciela S. Alarcón
Timothy J. Vyse
Joan T. Merrill
R. Hal Scofield
Philip Cohen
Source :
Repositorio EdocUR-U. Rosario, Universidad del Rosario, instacron:Universidad del Rosario, Europe PubMed Central
Publication Year :
2013
Publisher :
Ovid Technologies (Wolters Kluwer Health), 2013.

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 aknockin mouse expressinganin active 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 ofsystemic 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. Copyright © 2013 by the American Society of Nephrology.

Details

ISSN :
10466673
Volume :
24
Database :
OpenAIRE
Journal :
Journal of the American Society of Nephrology
Accession number :
edsair.doi.dedup.....9bf2a80f1d8b8333207ce678190e3280
Full Text :
https://doi.org/10.1681/asn.2013020148