Department of Immunology, Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Consejo Superior de Investigaciones Científicas, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento s/n 18100-Armilla, Granada, Spain.
Ann Rheum Dis. 2013 Apr;72(4):602-7. doi: 10.1136/annrheumdis-2012-201888. Epub 2012 Aug 15.
A recent genome-wide association study in European systemic sclerosis (SSc) patients identified three loci (PSORS1C1, TNIP1 and RHOB) as novel genetic risk factors for the disease. The aim of this study was to replicate the previously mentioned findings in a large multicentre independent SSc cohort of Caucasian ancestry.
4389 SSc patients and 7611 healthy controls from different European countries and the USA were included in the study. Six single nucleotide polymorphisms (SNP): rs342070, rs13021401 (RHOB), rs2233287, rs4958881, rs3792783 (TNIP1) and rs3130573 (PSORS1C1) were analysed. Overall significance was calculated by pooled analysis of all the cohorts. Haplotype analyses and conditional logistic regression analyses were carried out to explore further the genetic structure of the tested loci.
Pooled analyses of all the analysed SNPs in TNIP1 revealed significant association with the whole disease (rs2233287 p(MH)=1.94×10(-4), OR 1.19; rs4958881 p(MH)=3.26×10(-5), OR 1.19; rs3792783 p(MH)=2.16×10(-4), OR 1.19). These associations were maintained in all the subgroups considered. PSORS1C1 comparison showed association with the complete set of patients and all the subsets except for the anti-centromere-positive patients. However, the association was dependent on different HLA class II alleles. The variants in the RHOB gene were not associated with SSc or any of its subsets.
These data confirmed the influence of TNIP1 on an increased susceptibility to SSc and reinforced this locus as a common autoimmunity risk factor.
最近一项针对欧洲系统性硬化症（SSc）患者的全基因组关联研究发现了三个新的遗传风险位点（PSORS1C1、TNIP1 和 RHOB）。本研究的目的是在一个大型、多中心的、欧洲裔白种人独立 SSc 队列中对上述发现进行复制。
本研究共纳入来自不同欧洲国家和美国的 4389 名 SSc 患者和 7611 名健康对照。分析了 6 个单核苷酸多态性（SNP）：rs342070、rs13021401（RHOB）、rs2233287、rs4958881、rs3792783（TNIP1）和 rs3130573（PSORS1C1）。通过对所有队列的汇总分析计算总体显著性。进行单体型分析和条件逻辑回归分析，以进一步探讨所检测位点的遗传结构。
TNIP1 中所有分析 SNP 的汇总分析显示与整个疾病存在显著相关性（rs2233287 p(MH)=1.94×10(-4)，OR 1.19；rs4958881 p(MH)=3.26×10(-5)，OR 1.19；rs3792783 p(MH)=2.16×10(-4)，OR 1.19）。这些关联在考虑的所有亚组中均得到维持。PSORS1C1 的比较显示与所有患者和除抗着丝点阳性患者以外的所有亚组存在关联。然而，这种关联依赖于不同的 HLA Ⅱ类等位基因。RHOB 基因中的变体与 SSc 或其任何亚组均无关联。
这些数据证实了 TNIP1 对 SSc 易感性增加的影响，并强化了该位点作为一个常见的自身免疫风险因素。
