Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, University of Milan. [corrected]
Ann Rheum Dis. 2011 Apr;70(4):638-41. doi: 10.1136/ard.2010.141838. Epub 2010 Dec 27.
The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features.
A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers.
A pooled analysis revealed the association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI 1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant association of the four tested variants with patients with limited cutaneous SSc (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91, 95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR 1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904 minor alleles with patients positive for anti-centromere antibodies (ACA) remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25; OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR 0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to 0.97, respectively) and revealed a new risk haplotype associated with the same groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively).
The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.
本研究旨在证实 TNFSF4 多态性对系统性硬化症（SSc）易感性和表型特征的影响。
共纳入 8 个欧洲白种人族群，包括 3014 例 SSc 患者和 3125 名健康对照。选择 TNFSF4 基因启动子的 4 个遗传变异（rs1234314、rs844644、rs844648 和 rs12039904）作为遗传标志物。
汇总分析显示 rs1234314 和 rs12039904 多态性与 SSc 相关（OR 1.15，95%CI 1.02 至 1.31；OR 1.18，95%CI 1.08 至 1.29）。四项检测变异与局限性皮肤 SSc（lcSSc）患者的显著相关性得到揭示（rs1234314 OR 1.22，95%CI 1.07 至 1.38；rs844644 OR 0.91，95%CI 0.83 至 0.99；rs844648 OR 1.10，95%CI 1.01 至 1.20；rs12039904 OR 1.20，95%CI 1.09 至 1.33）。rs1234314、rs844648 和 rs12039904 次要等位基因与抗着丝点抗体（ACA）阳性患者的相关性仍然显著（OR 1.23，95%CI 1.10 至 1.37；OR 1.12，95%CI 1.01 至 1.25；OR 1.22，95%CI 1.07 至 1.38）。单体型分析证实了与 SSc、lcSSc 和 ACA 阳性亚组相关的保护性单体型（OR 0.88，95%CI 0.82 至 0.96；OR 0.88，95%CI 0.80 至 0.96；OR 0.86，95%CI 0.77 至 0.97），并揭示了与相同患者群体相关的新风险单体型（OR 1.14，95%CI 1.03 至 1.26；OR 1.20，95%CI 1.08 至 1.35；OR 1.23，95%CI 1.07 至 1.42）。
数据证实了 TNFSF4 多态性对 SSc 遗传易感性的影响，特别是在 lcSSc 和 ACA 阳性患者亚组中。
