类风湿关节炎易感性中核因子-κB的反馈抑制剂TNFAIP3及相邻基因间6q23区域的分析。

Analysis of TNFAIP3, a feedback inhibitor of nuclear factor-kappaB and the neighbor intergenic 6q23 region in rheumatoid arthritis susceptibility.

作者信息

Dieguez-Gonzalez Rebeca, Calaza Manuel, Perez-Pampin Eva, Balsa Alejandro, Blanco Francisco J, Cañete Juan D, Caliz Rafael, Carreño Luis, de la Serna Arturo R, Fernandez-Gutierrez Benjamin, Ortiz Ana Maria, Herrero-Beaumont Gabriel, Pablos Jose L, Narvaez Javier, Navarro Federico, Marenco Jose L, Gomez-Reino Juan J, Gonzalez Antonio

机构信息

Laboratorio de Investigacion 2 and Rheumatology Unit, Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain.

出版信息

Arthritis Res Ther. 2009;11(2):R42. doi: 10.1186/ar2650. Epub 2009 Mar 17.

DOI:10.1186/ar2650

PMID:19292917

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2688189/

Abstract

INTRODUCTION

Genome-wide association studies of rheumatoid arthritis (RA) have identified an association of the disease with a 6q23 region devoid of genes. TNFAIP3, an RA candidate gene, flanks this region, and polymorphisms in both the TNFAIP3 gene and the intergenic region are associated with systemic lupus erythematosus. We hypothesized that there is a similar association with RA, including polymorphisms in TNFAIP3 and the intergenic region.

METHODS

To test this hypothesis, we selected tag-single nucleotide polymorphisms (SNPs) in both loci. They were analyzed in 1,651 patients with RA and 1,619 control individuals of Spanish ancestry.

RESULTS

Weak evidence of association was found both in the 6q23 intergenic region and in the TNFAIP3 locus. The rs582757 SNP and a common haplotype in the TNFAIP3 locus exhibited association with RA. In the intergenic region, two SNPs were associated, namely rs609438 and rs13207033. The latter was only associated in patients with anti-citrullinated peptide antibodies. Overall, statistical association was best explained by the interdependent contribution of SNPs from the two loci TNFAIP3 and the 6q23 intergenic region.

CONCLUSIONS

Our data are consistent with the hypothesis that several RA genetic factors exist in the 6q23 region, including polymorphisms in the TNFAIP3 gene, like that previously described for systemic lupus erythematosus.

摘要

引言

类风湿关节炎（RA）的全基因组关联研究已确定该疾病与一个无基因的6q23区域存在关联。RA候选基因TNFAIP3位于该区域两侧，并且TNFAIP3基因和基因间区域的多态性均与系统性红斑狼疮相关。我们推测RA也存在类似的关联，包括TNFAIP3和基因间区域的多态性。

方法

为验证这一假设，我们在两个位点选择了标签单核苷酸多态性（SNP）。对1651例RA患者和1619名西班牙裔对照个体进行了分析。

结果

在6q23基因间区域和TNFAIP3位点均发现了较弱的关联证据。rs582757 SNP以及TNFAIP3位点的一个常见单倍型与RA相关。在基因间区域，有两个SNP与之相关，即rs609438和rs13207033。后者仅在抗瓜氨酸化肽抗体阳性的患者中相关。总体而言，两个位点TNFAIP3和6q23基因间区域的SNP相互依赖的作用最能解释这种统计学关联。