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.

A TNFSF13B Functional Variant Is Not Involved in Systemic Sclerosis and Giant Cell Arteritis Susceptibility / Gonzalez-Serna D.; Carmona E.G.; Ortego-Centeno N.; Simeon C.P.; Solans R.; Hernandez-Rodriguez J.; Tolosa C.; Castaneda S.; Narvaez J.; Martinez-Valle F.; Witte T.; Neumann T.; Holle J.; Beretta L.; Boiardi L.; Emmi G.; Cimmino M.A.; Vaglio A.; Herrick A.L.; Denton C.P.; Salvarani C.; Cid M.C.; Morgan A.W.; Fonseca C.; Gonzalez-Gay M.A.; Martin J.; Marquez A.. - In: PLOS ONE. - ISSN 1932-6203. - ELETTRONICO. - 13:(2018), pp. 1-12. [10.1371/journal.pone.0209343]

A TNFSF13B Functional Variant Is Not Involved in Systemic Sclerosis and Giant Cell Arteritis Susceptibility

Narvaez J.;Emmi G.;Vaglio A.;Martin J.;
2018

Abstract

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.
2018
13
1
12
Goal 3: Good health and well-being for people
Gonzalez-Serna D.; Carmona E.G.; Ortego-Centeno N.; Simeon C.P.; Solans R.; Hernandez-Rodriguez J.; Tolosa C.; Castaneda S.; Narvaez J.; Martinez-Vall...espandi
File in questo prodotto:
File Dimensione Formato  
journal.pone.0209343.pdf

accesso aperto

Tipologia: Pdf editoriale (Version of record)
Licenza: Open Access
Dimensione 557.36 kB
Formato Adobe PDF
557.36 kB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1197241
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 5
  • ???jsp.display-item.citation.isi??? 4
social impact