Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large trans-ethnic meta-analysis

Background: BANK1 and BLK belong to the pleiotropic autoimmune genes; recently, epistasis between BANK1 and BLK was detected in systemic lupus erythematosus. Although BLK has been reproducibly identified as a risk factor in rheumatoid arthritis (RA), reports are conflicting about the contribution of...

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Autores: Génin, Emmanuele, Coustet, Baptiste, Allanore, Yannick, Ito, Ikue, Teruel, María, Constantin, Arnaud, Schaeverbeke, Thierry, Ruyssen-Witrand, Adeline, Tohma, Shigeto, Cantagrel, Alain, Vittecoq, Olivier, Barnetche, Thomas, Le Loët, Xavier, Fardellone, Patrice, Furukawa, Hiroshi, Meyer, Olivier, Fernández-Gutiérrez, Benjamin, Balsa, Alejandro, González-Gay Mantecón, Miguel Ángel, Chiocchia, Gilles
Tipo de recurso: artículo
Fecha de publicación:2013
País:España
Institución:Universidad de Cantabria (UC)
Repositorio:UCrea Repositorio Abierto de la Universidad de Cantabria
Idioma:inglés
OAI Identifier:oai:repositorio.unican.es:10902/31350
Acceso en línea:https://hdl.handle.net/10902/31350
Access Level:acceso abierto
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spelling Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large trans-ethnic meta-analysisGénin, EmmanueleCoustet, BaptisteAllanore, YannickIto, IkueTeruel, MaríaConstantin, ArnaudSchaeverbeke, ThierryRuyssen-Witrand, AdelineTohma, ShigetoCantagrel, AlainVittecoq, OlivierBarnetche, ThomasLe Loët, XavierFardellone, PatriceFurukawa, HiroshiMeyer, OlivierFernández-Gutiérrez, BenjaminBalsa, AlejandroGonzález-Gay Mantecón, Miguel ÁngelChiocchia, GillesBackground: BANK1 and BLK belong to the pleiotropic autoimmune genes; recently, epistasis between BANK1 and BLK was detected in systemic lupus erythematosus. Although BLK has been reproducibly identified as a risk factor in rheumatoid arthritis (RA), reports are conflicting about the contribution of BANK1 to RA susceptibility. To ascertain the real impact of BANK1 on RA genetic susceptibility, we performed a large meta-analysis including our original data and tested for an epistatic interaction between BANK1 and BLK in RA susceptibility. Patients and Methods: We investigated data for 1,915 RA patients and 1,915 ethnically matched healthy controls genotyped for BANK1 rs10516487 and rs3733197 and BLK rs13277113. The association of each SNP and RA was tested by logistic regression. Multivariate analysis was then used with an interaction term to test for an epistatic interaction between the SNPs in the 2 genes. Results: None of the SNPs tested individually was significantly associated with RA in the genotyped samples. However, we detected an epistatic interaction between BANK1 rs3733197 and BLK rs13277113 (Pinteraction = 0.037). In individuals carrying the BLK rs13277113 GG genotype, presence of the BANK1 rs3733197 G allele increased the risk of RA (odds ratio 1.21 [95% confidence interval 1.04?1.41], P = 0.015. Combining our results with those of all other studies in a large trans-ethnic metaanalysis revealed an association of the BANK1 rs3733197 G allele and RA (1.11 [1.02?1.21], P = 0.012). Conclusion: This study confirms BANK1 as an RA susceptibility gene and for the first time provides evidence for epistasis between BANK1 and BLK in RA. Our results illustrate the concept of pleiotropic epistatic interaction, suggesting that BANK1 and BLK might play a role in RA pathogenesis.This work was partially funded by the RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III, within the VI PN de I+D+i 2008–2011. Unrestricted grant from PFIZER, ROCHE, ABBOTT, UCB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Public Library of ScienceUniversidad de Cantabria20132013-01-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttps://hdl.handle.net/10902/31350PLoS One, 2013, 8(4), e61044reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.unican.es:10902/313502026-06-02T12:39:31Z
dc.title.none.fl_str_mv Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large trans-ethnic meta-analysis
title Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large trans-ethnic meta-analysis
spellingShingle Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large trans-ethnic meta-analysis
Génin, Emmanuele
title_short Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large trans-ethnic meta-analysis
title_full Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large trans-ethnic meta-analysis
title_fullStr Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large trans-ethnic meta-analysis
title_full_unstemmed Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large trans-ethnic meta-analysis
title_sort Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large trans-ethnic meta-analysis
dc.creator.none.fl_str_mv Génin, Emmanuele
Coustet, Baptiste
Allanore, Yannick
Ito, Ikue
Teruel, María
Constantin, Arnaud
Schaeverbeke, Thierry
Ruyssen-Witrand, Adeline
Tohma, Shigeto
Cantagrel, Alain
Vittecoq, Olivier
Barnetche, Thomas
Le Loët, Xavier
Fardellone, Patrice
Furukawa, Hiroshi
Meyer, Olivier
Fernández-Gutiérrez, Benjamin
Balsa, Alejandro
González-Gay Mantecón, Miguel Ángel
Chiocchia, Gilles
author Génin, Emmanuele
author_facet Génin, Emmanuele
Coustet, Baptiste
Allanore, Yannick
Ito, Ikue
Teruel, María
Constantin, Arnaud
Schaeverbeke, Thierry
Ruyssen-Witrand, Adeline
Tohma, Shigeto
Cantagrel, Alain
Vittecoq, Olivier
Barnetche, Thomas
Le Loët, Xavier
Fardellone, Patrice
Furukawa, Hiroshi
Meyer, Olivier
Fernández-Gutiérrez, Benjamin
Balsa, Alejandro
González-Gay Mantecón, Miguel Ángel
Chiocchia, Gilles
author_role author
author2 Coustet, Baptiste
Allanore, Yannick
Ito, Ikue
Teruel, María
Constantin, Arnaud
Schaeverbeke, Thierry
Ruyssen-Witrand, Adeline
Tohma, Shigeto
Cantagrel, Alain
Vittecoq, Olivier
Barnetche, Thomas
Le Loët, Xavier
Fardellone, Patrice
Furukawa, Hiroshi
Meyer, Olivier
Fernández-Gutiérrez, Benjamin
Balsa, Alejandro
González-Gay Mantecón, Miguel Ángel
Chiocchia, Gilles
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad de Cantabria
description Background: BANK1 and BLK belong to the pleiotropic autoimmune genes; recently, epistasis between BANK1 and BLK was detected in systemic lupus erythematosus. Although BLK has been reproducibly identified as a risk factor in rheumatoid arthritis (RA), reports are conflicting about the contribution of BANK1 to RA susceptibility. To ascertain the real impact of BANK1 on RA genetic susceptibility, we performed a large meta-analysis including our original data and tested for an epistatic interaction between BANK1 and BLK in RA susceptibility. Patients and Methods: We investigated data for 1,915 RA patients and 1,915 ethnically matched healthy controls genotyped for BANK1 rs10516487 and rs3733197 and BLK rs13277113. The association of each SNP and RA was tested by logistic regression. Multivariate analysis was then used with an interaction term to test for an epistatic interaction between the SNPs in the 2 genes. Results: None of the SNPs tested individually was significantly associated with RA in the genotyped samples. However, we detected an epistatic interaction between BANK1 rs3733197 and BLK rs13277113 (Pinteraction = 0.037). In individuals carrying the BLK rs13277113 GG genotype, presence of the BANK1 rs3733197 G allele increased the risk of RA (odds ratio 1.21 [95% confidence interval 1.04?1.41], P = 0.015. Combining our results with those of all other studies in a large trans-ethnic metaanalysis revealed an association of the BANK1 rs3733197 G allele and RA (1.11 [1.02?1.21], P = 0.012). Conclusion: This study confirms BANK1 as an RA susceptibility gene and for the first time provides evidence for epistasis between BANK1 and BLK in RA. Our results illustrate the concept of pleiotropic epistatic interaction, suggesting that BANK1 and BLK might play a role in RA pathogenesis.
publishDate 2013
dc.date.none.fl_str_mv 2013
2013-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10902/31350
url https://hdl.handle.net/10902/31350
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv PLoS One, 2013, 8(4), e61044
reponame:UCrea Repositorio Abierto de la Universidad de Cantabria
instname:Universidad de Cantabria (UC)
instname_str Universidad de Cantabria (UC)
reponame_str UCrea Repositorio Abierto de la Universidad de Cantabria
collection UCrea Repositorio Abierto de la Universidad de Cantabria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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