Fine mapping of the MHC Class III region demonstrates association of AIF1 and rheumatoid arthritis

Harney, S; Vilariño‐Güell, Carles; Adamopoulos, Iannis E.; Sims, A. M.; Lawrence, Rw W.; Cardon, L R; Newton, JL; Meisel, Christian; Pointon, J J; Darke, C.; Athanasou, N A; Wordsworth, B P; Brown, Matthew A.

doi:10.1093/rheumatology/ken376

Cited by 41 publications

(25 citation statements)

References 20 publications

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“…However, it is intriguing that rs3132453 and additional PRRC2A SNPs are associated with other immune-related diseases such as rheumatoid arthritis 23 and atopic asthma. 24 Despite several disease associations with SNPs in or near PRRC2A, the gene's biologic function remains largely unknown. More is known of the involvement of a nearby apoptotic regulator gene, BAG6 (BAT3), in immune function and tumorigenesis.…”

Section: Rows 8 and 9)mentioning

confidence: 99%

PRRC2A and BCL2L11 gene variants influence risk of non-Hodgkin lymphoma: results from the InterLymph consortium

Nieters

Conde

Slager

et al. 2012

Blood

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Many common genetic variants have been associated with non-Hodgkin lymphoma (NHL), but individual study results are often conflicting. To confirm the role of putative risk alleles in B-cell NHL etiology, we performed a validation genotyping study of 67 candidate single nucleotide polymorphisms within InterLymph, a large international consortium of NHL case-control studies. A meta-analysis was performed on data from 5633 B-cell NHL cases and 7034 controls from 8 InterLymph studies. rs3789068 in the proapoptotic BCL2L11 gene was associated with an increased risk for B-cell NHL (odds ratio ‫؍‬ 1.21, P random ‫؍‬ 2.21 ؋ 10 ؊11 ), with similar risk estimates for common B-cell subtypes. PRRC2A rs3132453 in the HLA complex class III region conferred a reduced risk of B-cell NHL (odds ratio ‫؍‬ 0.68, P random ‫؍‬ 1.07 ؋ 10 ؊9 ) and was likewise evident for common B-cell subtypes. These results are consistent with the known biology of NHL and provide insights into shared pathogenic components, including apoptosis and immune regulation, for the major B-cell lymphoma subtypes. (Blood. 2012;120(23): 4645-4648) IntroductionNon-Hodgkin lymphoma (NHL) comprises a heterogeneous group of malignancies of lymphoid tissues. Familial aggregations 1 and NHL candidate gene and genome-wide association studies support the influence of common gene variants on NHL risk. [2][3][4][5][6][7] We conducted a validation study within the large international consortium of lymphoma, InterLymph, to confirm associations of 67 putative B-cell NHL risk alleles previously identified in smaller studies through a meta-analysis of 5633 B-cell NHL cases and 7034 controls. Methods Participating InterLymph studiesData were made available from the British Columbia NHL study 8 ; the Connecticut Women's NHL Study from Yale University 9 ; the European EpiLymph multicenter study 10 ; the Mayo Clinic NHL study 11 ; the National Cancer Institute/Surveillance, Epidemiology, and End Results Multi-Center Case-Control Study (NCI-SEER) 12 ; the New South Wales (NSW) lymphoma study 13 ; and the University of California, San Francisco (UCSF1)/ For personal use only. on May 11, 2018. by guest www.bloodjournal. org FromUniversity of California, Berkeley (UCSF2) studies of NHL 14,15 (supplemental Table 1, available on the Blood Web site; see the Supplemental Materials link at the top of the online article). Demographic data, including age at diagnosis for cases and age at interview for controls, sex, self-reported race and Hispanic/Latino ethnicity, HIV status, histologic subtype classification and/or International Classification of Diseases for Oncology code for lymphoma diagnoses, and genotype data were obtained for each study.Cases were diagnosed with incident lymphoma between 1989 and 2008. Analyses were restricted to participants Ն 18 years of age who were HIV-negative, non-Hispanic whites diagnosed with B-cell NHL. Histologic subtypes were grouped for analyses using the pathology coding scheme developed by InterLymph collaborators and pathologists based on the current ...

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Section: Rows 8 and 9)mentioning

confidence: 99%

PRRC2A and BCL2L11 gene variants influence risk of non-Hodgkin lymphoma: results from the InterLymph consortium

Nieters

Conde

Slager

et al. 2012

Blood

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“…A variety of diseases, ranging from cancer to autoimmune disorders and diabetes, are linked to Bag6 (33)(34)(35)(36)(37). Despite this demonstrated importance, structural characterization of the Bag6 complex is lacking.…”

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confidence: 99%

Bag6 complex contains a minimal tail-anchor–targeting module and a mock BAG domain

Mock

Chartron

Zaslaver

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

129

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BCL2-associated athanogene cochaperone 6 (Bag6) plays a central role in cellular homeostasis in a diverse array of processes and is part of the heterotrimeric Bag6 complex, which also includes ubiquitin-like 4A (Ubl4A) and transmembrane domain recognition complex 35 (TRC35). This complex recently has been shown to be important in the TRC pathway, the mislocalized protein degradation pathway, and the endoplasmic reticulum-associated degradation pathway. Here we define the architecture of the Bag6 complex, demonstrating that both TRC35 and Ubl4A have distinct C-terminal binding sites on Bag6 defining a minimal Bag6 complex. A crystal structure of the Bag6–Ubl4A dimer demonstrates that Bag6–BAG is not a canonical BAG domain, and this finding is substantiated biochemically. Remarkably, the minimal Bag6 complex defined here facilitates tail-anchored substrate transfer from small glutamine-rich tetratricopeptide repeat-containing protein α to TRC40. These findings provide structural insight into the complex network of proteins coordinated by Bag6.

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“…In another study, we have shown that the AIF1 rs2259571 CC genotype is associated with active form of RA. 7 The important role of AIF1 gene polymorphisms in RA pathogenesis was indicated in a study by Harney et al 12 which examined the AIF1 gene rs2269475 and rs2259571 polymorphisms in RA patients. These authors have shown a significant association between RA and AIF1 haplotypes independent of human leukocyte antigen-DRB1 (HLA-DRB1).…”

Section: Discussionmentioning

confidence: 99%

AIF1 Gene RS2269475:C>T Polymorphism is Associated With Rheumatoid Arthritis Development but not With Disease Activity

et al. 2015

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Fine mapping of the MHC Class III region demonstrates association of AIF1 and rheumatoid arthritis

Abstract: The results of the genotyping and expression studies presented here suggest a role for AIF1 in both the aetiology and pathogenesis of RA.

Cited by 41 publications

References 20 publications

PRRC2A and BCL2L11 gene variants influence risk of non-Hodgkin lymphoma: results from the InterLymph consortium

PRRC2A and BCL2L11 gene variants influence risk of non-Hodgkin lymphoma: results from the InterLymph consortium

Bag6 complex contains a minimal tail-anchor–targeting module and a mock BAG domain

AIF1 Gene RS2269475:C>T Polymorphism is Associated With Rheumatoid Arthritis Development but not With Disease Activity

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