TY - JOUR
T1 - A TNFSF13B functional variant is not involved in systemic sclerosis and giant cell arteritis susceptibility
AU - European GCA Consortium
AU - European Scleroderma Group
AU - González-Serna, David
AU - Carmona, Elio G.
AU - Ortego-Centeno, Norberto
AU - Simeón, Carmen P.
AU - Solans, Roser
AU - Hernández-Rodríguez, José
AU - Tolosa, Carlos
AU - Castañeda, Santos
AU - Narváez, Javier
AU - Martinez-Valle, Ferran
AU - Witte, Torsten
AU - Neumann, Thomas
AU - Holle, Julia
AU - Beretta, Lorenzo
AU - Boiardi, Luigi
AU - Emmi, Giacomo
AU - Cimmino, Marco A.
AU - Vaglio, Augusto
AU - Herrick, Ariane L.
AU - Denton, Christopher P.
AU - Salvarani, Carlo
AU - Cid, María C.
AU - Morgan, Ann W.
AU - Fonseca, Carmen
AU - González-Gay, Miguel A.
AU - Martín, Javier
AU - Márquez, Ana
PY - 2018/1/1
Y1 - 2018/1/1
N2 - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Our data suggest that the TNFSF13B functional variant does not contribute to the genetic network underlying GCA and SSc.
AB - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Our data suggest that the TNFSF13B functional variant does not contribute to the genetic network underlying GCA and SSc.
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U2 - 10.1371/journal.pone.0209343
DO - 10.1371/journal.pone.0209343
M3 - Article
C2 - 30586461
AN - SCOPUS:85059233125
VL - 13
SP - e0209343
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 12
ER -