title: ABIN1 dysfunction as a genetic basis for lupus nephritis.
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)-κB 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-κB 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-κB and mitogen-activated protein kinase activity.
authors: Departments of Medicine.
authors: Dawn J
authors: DJ
authors: Caster
authors: Erik A
authors: EA
authors: Korte
authors: Sambit K
authors: SK
authors: Nanda
authors: Kenneth R
authors: KR
authors: McLeish
authors: Rebecca K
authors: RK
authors: Oliver
authors: Rachel T
authors: RT
authors: G'sell
authors: Ryan M
authors: RM
authors: Sheehan
authors: Darrell W
authors: DW
authors: Freeman
authors: Susan C
authors: SC
authors: Coventry
authors: Jennifer A
authors: JA
authors: Kelly
authors: Joel M
authors: JM
authors: Guthridge
authors: Judith A
authors: JA
authors: James
authors: Kathy L
authors: KL
authors: Sivils
authors: Marta E
authors: ME
authors: Alarcon-Riquelme
authors: R Hal
authors: RH
authors: Scofield
authors: Indra
authors: I
authors: Adrianto
authors: Patrick M
authors: PM
authors: Gaffney
authors: Anne M
authors: AM
authors: Stevens
authors: Barry I
authors: BI
authors: Freedman
authors: Carl D
authors: CD
authors: Langefeld
authors: Betty P
authors: BP
authors: Tsao
authors: Bernardo A
authors: BA
authors: Pons-Estel
authors: Chaim O
authors: CO
authors: Jacob
authors: Diane L
authors: DL
authors: Kamen
authors: Gary S
authors: GS
authors: Gilkeson
authors: Elizabeth E
authors: EE
authors: Brown
authors: Graciela S
authors: GS
authors: Alarcon
authors: Jeffrey C
authors: JC
authors: Edberg
authors: Robert P
authors: RP
authors: Kimberly
authors: Javier
authors: J
authors: Martin
authors: Joan T
authors: JT
authors: Merrill
authors: John B
authors: JB
authors: Harley
authors: Kenneth M
authors: KM
authors: Kaufman
authors: John D
authors: JD
authors: Reveille
authors: Juan-Manuel
authors: JM
authors: Anaya
authors: Lindsey A
authors: LA
authors: Criswell
authors: Luis M
authors: LM
authors: Vila
authors: Michelle
authors: M
authors: Petri
authors: Rosalind
authors: R
authors: Ramsey-Goldman
authors: Sang-Cheol
authors: SC
authors: Bae
authors: Susan A
authors: SA
authors: Boackle
authors: Timothy J
authors: TJ
authors: Vyse
authors: Timothy B
authors: TB
authors: Niewold
authors: Philip
authors: P
authors: Cohen
authors: David W
authors: DW
authors: Powell
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D008181:Lupus Nephritis / Q000209:etiology / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000502:physiology; D020641:Polymorphism, Single Nucleotide
chemical_list: D004268:DNA-Binding Proteins; D016328:NF-kappa B; C117046:TNIP1 protein, human
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