一个 TNFSF13B 功能变体与系统性硬化症和巨细胞动脉炎易感性无关。
A TNFSF13B functional variant is not involved in systemic sclerosis and giant cell arteritis susceptibility.
机构信息
Instituto de Parasitología y Biomedicina "López-Neyra", CSIC, PTS Granada, Granada, Spain.
Systemic Autoimmune Diseases Unit, Hospital Clínico San Cecilio, Granada, Spain.
出版信息
PLoS One. 2018 Dec 26;13(12):e0209343. doi: 10.1371/journal.pone.0209343. eCollection 2018.
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.
背景
TNFSF13B（肿瘤坏死因子超家族成员 13b）基因编码 BAFF，BAFF 在 B 细胞的分化和激活中起着至关重要的作用。该基因的一个插入-缺失变异（GCTGT→A），导致 BAFF 水平升高，最近与多种自身免疫性疾病（包括多发性硬化症、系统性红斑狼疮和类风湿关节炎）的遗传易感性有关。基于巨细胞动脉炎（GCA）和系统性硬化症（SSc）患者中发现的这种细胞因子水平升高，我们旨在评估该功能变体是否也是这两种疾病的新遗传危险因素。
方法
共纳入来自 4 个欧洲队列的 1728 例活检证实的 GCA 患者、来自 3 个欧洲队列的 4584 例 SSc 患者和 5160 名匹配的健康对照者。使用定制的 TaqMan 检测对与先前自身免疫性疾病相关的遗传变异密切相关的单核苷酸多态性（SNP）rs374039502 进行基因分型。首先，使用 Plink（v1.9）中的 χ2 检验在每个独立队列中进行关联分析。随后，通过逆方差法对不同的病例/对照集进行荟萃分析。
结果
在任何分析队列中，与对照组相比，病例组的等位基因分布均无统计学差异。同样，不同组的合并分析也证明 rs374039502 变异与 GCA（P=0.421；OR（95%CI）=0.92（0.75-1.13））和 SSc（P=0.500；OR（95%CI）=1.05（0.91-1.22））无关联。考虑到这些疾病主要临床亚表型的分层分析得出了类似的阴性结果。
结论
我们的数据表明，TNFSF13B 功能变体不会导致 GCA 和 SSc 的遗传网络发生变化。
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