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

Abstract: 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.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: PLoS One, 2013, 8(4), e61044

Editorial: Public Library of Science

 Año de publicación: 2013

Nº de páginas: 8

Tipo de publicación: Artículo de Revista

 DOI: 10.1371/journal.pone.0061044

ISSN: 1932-6203

Url de la publicación: https://doi.org/10.1371/journal.pone.0061044

Autoría

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