A TNFSF13B functional variant is not involved in systemic sclerosis and giant cell arteritis susceptibility

• Published in: PloS one Vol. 13; no. 12; p. e0209343
• Main Authors: González-Serna, David, Carmona, Elio G, Ortego-Centeno, Norberto, Simeón, Carmen P, Solans, Roser, Hernández-Rodríguez, José, Tolosa, Carlos, Castañeda, Santos, Narváez, Javier, Martinez-Valle, Ferran, Witte, Torsten, Neumann, Thomas, Holle, Julia, Beretta, Lorenzo, Boiardi, Luigi, Emmi, Giacomo, Cimmino, Marco A, Vaglio, Augusto, Herrick, Ariane L, Denton, Christopher P, Salvarani, Carlo, Cid, María C, Morgan, Ann W, Fonseca, Carmen, González-Gay, Miguel A, Martín, Javier, Márquez, Ana
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.12.2018; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Aged, 80 and over; Arteritis; Arthritis; Association analysis; Autoimmune diseases; B cells; B-Cell Activating Factor - genetics; Binding sites; Biology and Life Sciences; Biomedical research; Biopsy; BLyS protein; Case-Control Studies; Cell activation; Chronic conditions; Clonal deletion; Cohort Studies; Consortia; Cytokines; Cèl·lules B; Europe; Female; Gene deletion; Gene expression; Gene polymorphism; Gene Regulatory Networks - genetics; Genetic aspects; Genetic diversity; Genetic Predisposition to Disease; Genetic variance; Genetic variation; Genotyping Techniques; Genètica molecular; Giant Cell Arteritis - genetics; Giant Cell Arteritis - pathology; Health aspects; Homeostasis; Hospitals; Humans; INDEL Mutation; Insertion; Internal medicine; Lymphocytes B; Male; Medicine; Medicine and Health Sciences; Middle Aged; Molecular genetics; Multiple sclerosis; Pathogenesis; Patients; Physical Sciences; Polymorphism; Polymorphism, Single Nucleotide; Research and Analysis Methods; Rheumatoid arthritis; Rheumatology; Risk analysis; Risk factors; Scleroderma; Scleroderma (Disease); Scleroderma, Systemic - genetics; Scleroderma, Systemic - pathology; Single-nucleotide polymorphism; Statistical analysis; Systemic diseases; Systemic lupus erythematosus; Systemic sclerosis; Temporal arteritis; Tumor necrosis factor-TNF; Vein & artery diseases; Europe; Italy; United Kingdom > UK; Germany; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0209343

The TNFSF13B (TNF superfamily member 13b) gene encodes BAFF, a cytokine with a crucial role in the differentiation and activation of B cells. An insertion-deletion variant (GCTGT→A) of this gene, leading to increased levels of BAFF, has been recently implicated in the genetic predisposition to several autoimmune diseases, including multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. Based on the elevated levels of this cytokine found in patients with giant cell arteritis (GCA) and systemic sclerosis (SSc), we aimed to assess whether this functional variant also represents a novel genetic risk factor for these two disorders. A total of 1,728 biopsy-proven GCA patients from 4 European cohorts, 4,584 SSc patients from 3 European cohorts and 5,160 ethnically-matched healthy controls were included in the study. The single nucleotide polymorphism (SNP) rs374039502, which colocalizes with the genetic variant previously implicated in autoimmunity, was genotyped using a custom TaqMan assay. First, association analysis was conducted in each independent cohort using χ2 test in Plink (v1.9). Subsequently, different case/control sets were meta-analyzed by the inverse variance method. No statistically significant differences were found when allele distributions were compared between cases and controls for any of the analyzed cohorts. Similarly, combined analysis of the different sets evidenced a lack of association of the rs374039502 variant with GCA (P = 0.421; OR (95% CI) = 0.92 (0.75-1.13)) and SSc (P = 0.500; OR (95% CI) = 1.05 (0.91-1.22)). The stratified analysis considering the main clinical subphenotypes of these diseases yielded similar negative results. Our data suggest that the TNFSF13B functional variant does not contribute to the genetic network underlying GCA and SSc.