Lookup NU author(s): Dr Jessica Tarn,
Dr James Locke,
Professor Fai Ng
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Background and objective A germline and coding polymorphism (rs2230926) of TNFAIP3 (A20), a central gatekeeper of nuclear factor-kappa B (NF-kB) activation, was recently found associated with primary Sjgren's syndrome (pSS)-associated lymphoma in a French cohort. We aimed to replicate this association.Patients and methods The rs2230926 polymorphism was genotyped in cases and controls of European ancestry from two independent cohorts from UK and France. Case control association tests were performed (Fisher's test) in the two cohorts, followed by a meta-analysis of the two cohorts.Results The UK cohort included 308 controls and 590 patients with pSS including 31 with a history of lymphoma. The French cohort consisted of 448 controls and 589 patients with pSS including 47 with lymphoma. In both cohorts, the rs2230926 missense polymorphism was not associated with pSS. However, in the UK cohort, the rs2230926G variant was significantly associated with pSS-associated lymphoma (OR = 2.74, 95% CI (1.07 to 7.03), p = 0.0423, compared with patients with pSS without lymphoma, and OR = 3.12, 95% CI (1.16 to 8.41), p = 0.0314, compared with healthy controls) as observed in the French cohort. The meta-analysis of the two cohorts confirmed these results (OR = 2.48, 95% CI (1.87 to 3.28) p = 0.0037 and OR = 2.60, 95% CI (1.91 to 3.53) p = 0.0031, respectively).Conclusions This study confirms the role of A20 impairment in pSS-associated lymphoma. Subtle germline abnormalities of genes leading to impaired control of NF-kB activation in B cells continuously stimulated by autoimmunity enhance the risk of lymphoma.
Author(s): Nocturne G, Tarn J, Boudaoud S, Locke J, Miceli-Richard C, Hachulla E, Dubost JJ, Bowman S, Gottenberg JE, Criswell LA, Lessard CJ, Sivils KL, Carapito R, Bahram S, Seror R, Ng WF, Mariette X
Publication type: Article
Publication status: Published
Journal: Annals of the Rheumatic Diseases
Print publication date: 01/04/2016
Online publication date: 02/09/2015
Acceptance date: 12/08/2015
ISSN (print): 0003-4967
ISSN (electronic): 1468-2060
Publisher: BMJ Group
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