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Abstract
A rare variant (BAFF-var) of the tumor necrosis factor superfamily 13b (TNFSF13B) gene has been recently associated with multiple sclerosis (MS) and systemic lupus erythematosus (SLE). The aim of this study was to investigate the association between TNFSF13B BAFF-var and susceptibility to rheumatoid arthritis (RA) and replicate that association in SLE. 6,218 RA patients, 2,575 SLE patients and 4,403 healthy controls from three different countries were included in the study. TNFSF13B BAFF-var was genotyped using TaqMan allelic discrimination assay. PLINK software was used for statistical analyses. TNFSF13B BAFF-var was significantly associated with RA (p = 0.015, OR = 1.21, 95% CI = 1.03–1.41) in the Spanish cohort. A trend of association was observed in the Dutch (p = 0.115) and German (p = 0.228) RA cohorts. A meta-analysis of the three RA cohorts included in this study revealed a statistically significant association (p = 0.002, OR = 1.24, 95% CI = 1.10–1.38). In addition, TNFSF13B BAFF-var was significantly associated with SLE in the Spanish (p = 0.001, OR = 1.41, 95% CI = 1.14–1.74) and the German cohorts (p = 0.030, OR = 1.86, 95% CI = 1.05–3.28), with a statistically significant p-value obtained in the meta-analysis (p = 0.0002, OR = 1.46, 95% CI = 1.09–2.32). The results obtained confirm the known association of TNFSF13B BAFF-var with SLE and, for the first time, demonstrate that this variant contributes to susceptibility to RA.
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1 Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain
2 Rheumatology Department, Hospital Virgen de las Nieves, Granada, Spain
3 Systemic Autoimmune Diseases Unit, Hospital Campus de la Salud, Granada, Spain
4 Rheumatology Service, Hospital Clínico San Carlos, IDISSC, Madrid, Spain
5 Rheumatology Service, Hospital General Universitario Gregorio Marañón, Madrid, Spain
6 Rheumatology Department, Instituto de Investigación Hospital Universitario La Paz (IDIPAZ), Madrid, Spain
7 Rheumatology Department, Instituto de Investigación del Hospital de La Princesa (IIS-IP), Madrid, Spain
8 Rheumatology Service, Hospital Universitario de Bellvitge, Barcelona, Spain
9 Systemic Autoimmune Diseases Unit, Department of Internal Medicine, Hospital Virgen de las Nieves, Granada, Spain
10 Rheumatology Department, Hospital Virgen de la Victoria, Málaga, Spain
11 Department of Immunology, Hospital Universitario Virgen del Rocío, IBIS, Sevilla, Spain
12 Department of Internal Medicine, Hospital Parc Taulí, Sabadell, Spain
13 Rheumatology Service, Hospital Universitario 12 de Octubre, Madrid, Spain
14 Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands
15 Department of Human Genetics, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands
16 Department for Clinical Immunology and Rheumatology, Hannover Medical School, Hannover, Germany
17 Policlinic and Hiller Research Unit for Rheumatology, UKD, Heinrich-Heine-University Dusseldorf, Dusseldorf, Germany
18 Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases IDIVAL, Hospital Universitario Marqués de Valdecilla, Santander, Spain