Publication

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

Journal Paper/Review - Dec 26, 2018

Units
PubMed
Doi

Citation
González-Serna D, Boiardi L, Emmi G, Cimmino M, Vaglio A, Herrick A, Denton C, Salvarani C, Cid M, Morgan A, Fonseca C, González-Gay M, Martín J, Beretta L, Holle J, Neumann T, Carmona E, Ortego-Centeno N, Simeón C, Solans R, Hernández-Rodríguez J, Tolosa C, Castañeda S, Narváez J, Martinez-Valle F, European GCA Consortium, European Scleroderma Group, Witte T, Márquez A. A TNFSF13B functional variant is not involved in systemic sclerosis and giant cell arteritis susceptibility. PloS one 2018; 13:e0209343.
Type
Journal Paper/Review (English)
Journal
PloS one 2018; 13
Publication Date
Dec 26, 2018
Issn Electronic
1932-6203
Pages
e0209343
Brief description/objective

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.