Hamdy Gehan, Darweesh Hanan, Khattab Enas A, Fawzy Samar, Fawzy Esmat, Sheta Marwa
Department of Internal Medicine, Faculty of Medicine, Kasr El Ani Hospital, Cairo University, Egypt.
Department of Rheumatology& Rehabilitation, Faculty of Medicine, Kasr El Ani Hospital, Cairo University, Egypt.
Hum Immunol. 2015 Jun;76(6):417-20. doi: 10.1016/j.humimm.2015.03.020. Epub 2015 Apr 7.
The identification of additional genetic risk factor is an on-going process that will aid in the understanding of rheumatoid arthritis (RA) aetiology. A genome-wide association scan in Crohn's (CD) disease highlighted the interleukin-23 receptor (IL23R) gene as a susceptibility factor. Since the IL-23/IL-17 pathway is known to associate with other autoimmune disease, including rheumatoid arthritis and systemic sclerosis, we hypothesised that IL23R could be a shared susceptibility gene. The rare allele of IL23R single nucleotide polymorphism (SNP) rs11209026 (Arg381Gln) confers strong protection against CD. Our aim was to analyse IL23R SNP (rs11209026, rs2201841, and rs10889677) and to detect its association with RA in Egyptian patients.
A group of Egyptian patients with RA (n=120) and apparently healthy persons as controls (n=120) was genotyped for rs11209026, rs2201841 and rs10889677 by real time/polymerase chain reaction (real-time/PCR) for the first SNP and restriction fragment length polymorphism/PCR (RFLP/PCR) in the last two SNPs.
Our data emphasise that the AA genotype of rs11209026 (Arg381Gln) was significantly associated with RA patients compared to the controls (P value=0.001).We did not find any significant association between either rs2201841 or rs10889677 and the development of rheumatoid arthritis (P value=1.000 & 0.562 respectively).
Our results suggest that IL23 receptor AA genotype variant of rs11209026 would contribute to RA aetiology; consequently, it might be a genetic marker for RA. We need to address the subgroup of patients who will benefit from the selective suppression of the IL23 signalling which would represent new perspectives toward a personalized therapy of RA patients by further studies.
识别更多的遗传风险因素是一个持续的过程，这将有助于理解类风湿关节炎（RA）的病因。一项针对克罗恩病（CD）的全基因组关联扫描突出了白细胞介素-23受体（IL23R）基因作为一个易感因素。由于已知IL-23/IL-17通路与包括类风湿关节炎和系统性硬化症在内的其他自身免疫性疾病相关，我们推测IL23R可能是一个共享的易感基因。IL23R单核苷酸多态性（SNP）rs11209026（Arg381Gln）的罕见等位基因对CD具有很强的保护作用。我们的目的是分析IL23R SNP（rs11209026、rs2201841和rs10889677）并检测其与埃及RA患者的关联。
通过实时/聚合酶链反应（实时/PCR）对第一个SNP rs11209026以及对后两个SNP采用限制性片段长度多态性/PCR（RFLP/PCR），对一组埃及RA患者（n = 120）和作为对照的明显健康者（n = 120）进行基因分型。
我们的数据强调，与对照组相比，rs11209026（Arg381Gln）的AA基因型与RA患者显著相关（P值 = 0.001）。我们未发现rs2201841或rs10889677与类风湿关节炎的发生之间存在任何显著关联（P值分别为1.000和0.562）。
我们的结果表明，rs11209026的IL23受体AA基因型变异可能与RA病因有关；因此，它可能是RA的一个遗传标记。我们需要通过进一步研究确定哪些患者亚组将从IL23信号通路的选择性抑制中获益，这将为RA患者的个性化治疗带来新的前景。
