Garnier Sophie, Dieudé Philippe, Michou Laetitia, Barbet Sandra, Tan Alice, Lasbleiz Sandra, Bardin Thomas, Prum Bernard, Cornélis François
GenHotel-EA3886, Laboratoire Européen de Recherche pour la Polyarthrite Rhumatoïde, 2 rue Gaston Crémieux, 91057 Evry-Genopole Cedex, France.
Ann Rheum Dis. 2007 Jun;66(6):828-31. doi: 10.1136/ard.2006.061390. Epub 2006 Dec 7.
Recently, a new genetic factor within the interferon regulatory factor 5 (IRF5) gene was demonstrated for systemic lupus erythematosus (SLE) through linkage and association: the rs2004640-T allele. IRF5 is involved in the production of rheumatoid arthritis (RA) cytokines, and SLE already shares with RA one genetic factor within the tyrosine phosphatase PTPN22 gene.
To test the hypothesis that the SLE IRF5 genetic factor could also be shared with RA.
100 French Caucasian trio families with RA were genotyped and analysed with the transmission disequilibrium test, the frequency comparison of the transmitted and untransmitted alleles, and the genotype relative risk. 97% power was available to detect at least a trend in favour of a factor similar to that reported for SLE.
The analysis showed the absence of linkage and association globally and in "autoimmune" RA subsets, with a weak non-significant trend against the IRF5 rs20046470-T allele. Given the robustness of familial-based analysis, this slight negative trend provided strong evidence against even a weaker factor than that reported for SLE.
Our results exclude the IRF5 rs2004640-T allele as a major genetic factor for RA in this French Caucasian population.
最近，通过连锁分析和关联研究在干扰素调节因子5（IRF5）基因中发现了一个与系统性红斑狼疮（SLE）相关的新遗传因子：rs2004640-T等位基因。IRF5参与类风湿关节炎（RA）细胞因子的产生，并且SLE已经与RA在酪氨酸磷酸酶PTPN22基因内共享一个遗传因子。
检验SLE的IRF5遗传因子也可能与RA共享的假设。
对100个患有RA的法裔高加索三人家庭进行基因分型，并采用传递不平衡检验、传递和未传递等位基因的频率比较以及基因型相对风险进行分析。有97%的把握度可检测到至少一种有利于类似于SLE报道因子的趋势。
分析表明，总体上以及在“自身免疫性”RA亚组中均不存在连锁和关联，对IRF5 rs20046470-T等位基因有微弱的非显著反向趋势。鉴于基于家族分析的稳健性，这种轻微的负向趋势提供了有力证据，排除了甚至比SLE报道的因子更弱的因子。
我们的结果排除了IRF5 rs2004640-T等位基因作为该法裔高加索人群中RA主要遗传因子的可能性。
