Session Title: Genetics and Genomics of Rheumatic Diseases
Session Type: Abstract Submissions (ACR)
Background/Purpose: BANK1 and BLK belong to pleiotropic genes and recently a genetic and physical interaction between BANK1 and BLK has been detected in systemic lupus erythematosus. Although BLK has been reproducibly identified as a RA risk factor, conflicting results have been reported regarding the contribution of BANK1 in RA susceptibility. To ascertain the real impact of BANK1 on RA genetic susceptibility we performed a large meta-analysis. In addition, we tested for an epistatic interaction between BLK and BANK1 in RA susceptibility.
Methods: We performed a large trans-ethnic meta-analysis including data from 8,898 RA patients and 15,479 controls genotyped for BANK1 rs10516487 and data from 3,641 RA cases and 3,710 controls genotyped for BANK1 rs3733197. BLK rs13277113 and BANK1 genotypes available from 1,901 RA patients and 1,898 ethnically matched controls coming from France, Spain and Japan were used to test for epistasis by logistic regression analysis.
Results: The meta-analysis provided evidence for an association between RA and BANK1 rs3733197 G risk allele (OR=1.11 95% CI[1.02–1.21], P=0.012). An epistatic interaction between BLK rs13277113 and BANK1 rs3733197 was detected (Pep=0.037). The association between the BANK1 rs3733197 G risk allele and RA was restricted to individuals carrying the BLK rs13277113 GG genotype: OR=1.21 95%CI[1.04-1.41], P=0.015
Conclusion: This study confirms BANK1 as a RA susceptibility gene and provides for the first time, evidence for epistasis between BLK and BANK1. Our results illustrate the concept of pleiotropic epistatic interaction suggesting that BLK and BANK1 might play a role in RA pathogenesis.
A. L. Constantin,
The work was supported by Research Grants from Daiwa Securities Health Foundation, Research Grants from Japan Research Foundation for Clinical Pharmacology, Research Grants from The Nakatomi Foundation, Research Grants from Takeda Science Foundation.,
M. A. González-Gay,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/epistatic-interaction-between-bank1-and-blk-in-rheumatoid-arthritis-results-from-a-large-trans-ethnic-meta-analysis/