CCR6作为系统性硬化症中抗拓扑异构酶I抗体风险因素的确认。

Confirmation of CCR6 as a risk factor for anti-topoisomerase I antibodies in systemic sclerosis.

作者信息

Ochoa Eguzkine, Martin José-Ezequiel, Assasi Shervin, Beretta Lorenzo, Carreira Patricia, Guillén Alfredo, Simeón Carmen Pilar, Koumakis Eugénie, Dieude Philippe, Allanore Yannick, García-Hernández Francisco J, Espinosa Gerard, Castellví Ivan, Trapiella Jose Luis, Rodriguez Luis, González-Gay Miguel Ángel, Egurbide María Victoria, Sáez Luis, Callejas-Rubio Jose Luis, Vargas-Hitos Jose Antonio, Hunzelmann Nicolas, Riemekasten Gabriela, Witte Torsten, Distler Jörg H W, Kreuter Alexander, Lunardi Claudio, Santaniello Alessandro, Tan Filemon K, Shiels Paul G, Herrick Ariane, Worthington Jane, Vonk Madelon C, Koeleman Bobby P, Radstake Timothy R D J, Mayes Maureen D, Martin Javier

机构信息

Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Granada, Spain.

The University of Texas Health Science Center-Houston, Houston, TX, USA.

出版信息

Clin Exp Rheumatol. 2015 Jul-Aug;33(4 Suppl 91):S31-5. Epub 2015 Aug 27.

PMID:26314374

Abstract

OBJECTIVES

The current knowledge of the influence of systemic sclerosis (SSc) risk loci in the clinical sub-phenotypes is still limited. The main limitation lies in the low frequency of some sub-phenotypes which could be solved by replication studies in independent cohorts and meta-analysis between studies. In this regard, CCR6 gene variants have been recently associated with anti-topoisomerase I positive (ATA+) production in SSc patients in a candidate gene study. This gene has been proposed to have a critical role in IL-17-driven autoimmunity in human diseases.

METHODS

In order to confirm the association between CCR6 and ATA+ SSc patients, we performed an independent replication study in populations of European ancestry. We studied two CCR6 genetic variants (rs968334 and rs3093024) in a total of 901 ATA+ SSc cases, 3,258 ATA- SSc cases and 7,865 healthy controls and compared allelic frequencies for those SNPs in ATA+ SSc with healthy controls and also with ATA- SSc patients.

RESULTS

The comparison performed between ATA+ SSc patients and healthy controls showed significant association with SNP rs968334 (p=4.88x10(-2), OR=1.11). When we compared ATA+ SSc cases with ATA- SSc, both SNPs, rs3093024 and rs968334, showed significant associations (p=2.89x10(-2), OR=1.13; p=1.69x10(-2), OR=1.15). Finally, in order to increase even more sample size and statistical power, we meta-analysed our study with the previous reported and found a significant association between SNP rs3093024 and ATA+ SSc patients (p=1.00x10(-4), OR=1.16) comparing with healthy controls.

CONCLUSIONS

Our work confirms the association of CCR6 gene and ATA+ SSc patients.

摘要

目的

目前关于系统性硬化症（SSc）风险基因座对临床亚表型影响的认识仍然有限。主要限制在于某些亚表型的频率较低，这可以通过在独立队列中进行重复研究以及研究间的荟萃分析来解决。在这方面，一项候选基因研究最近发现CCR6基因变异与SSc患者抗拓扑异构酶I阳性（ATA +）产生有关。该基因被认为在人类疾病中由IL - 17驱动的自身免疫中起关键作用。

方法

为了证实CCR6与ATA + SSc患者之间的关联，我们在欧洲血统人群中进行了一项独立的重复研究。我们研究了总共901例ATA + SSc病例、3258例ATA - SSc病例和7865例健康对照中的两个CCR6基因变异（rs968334和rs3093024），并比较了ATA + SSc患者与健康对照以及ATA - SSc患者中这些单核苷酸多态性（SNP）的等位基因频率。

结果

ATA + SSc患者与健康对照之间的比较显示，与SNP rs968334存在显著关联（p = 4.88×10（-2），OR = 1.11）。当我们将ATA + SSc病例与ATA - SSc进行比较时，rs3093024和rs968334这两个SNP均显示出显著关联（p = 2.89×10（-2），OR = 1.13；p = 1.69×10（-2），OR = 1.15）。最后，为了进一步增加样本量和统计效力，我们将我们的研究与先前报道的研究进行荟萃分析，发现与健康对照相比，SNP rs3093024与ATA + SSc患者之间存在显著关联（p = 1.00×10（-4），OR = 1.16）。