Hassine Hana Ben, Boumiza Asma, Sghiri Rim, Baccouche Khadija, Boussaid Imen, Atig Ahlem, Shakoor Zahid, Bouajina Elyes, Zemni Ramzi
1 Laboratory of Immunology , Research Unit UR 807, Faculty of Medicine of Sousse, Sousse, Tunisia .
2 Department of Rheumatology, Farhat Hached Hospital , Sousse, Tunisia .
Genet Test Mol Biomarkers. 2017 Feb;21(2):92-96. doi: 10.1089/gtmb.2016.0270.
Rheumatoid arthritis (RA) is characterized by the production of an array of proinflammatory cytokines through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Interleukin-1 receptor (IL-1R) and Toll-like receptors contain a common cytoplasmic motif the Toll/IL-1R (TIR) homology domain. This motif is required for NF-κB activation. IL-1R-associated kinase 1 (IRAK1) is a key adapter molecule recruited during the signaling cascade of the TIR. Its gene expression is regulated by the micro-RNA (miR)-146a.
We investigated the role of IRAK1 single-nucleotide polymorphism (SNP) rs3027898 (IRAK1 rs3027898) and miR-146a SNP rs2910164 (miR-146a rs2910164) in Tunisian patients with RA and their association with C reactive protein (CRP), rheumatoid factor (RF), anticyclic citrullinated peptide (anti-CCP) antibodies, and erosion.
In a cohort of 172 adult RA patients and 224 matched controls, IRAK1 rs3027898 genotyping was determined by mutagenically separated polymerase chain reaction (MS-PCR) with newly designed primers, and miR-146a rs2910164 genotyping was determined by fragment length polymorphism PCR-restriction (RFLP-PCR).
The IRAK1 rs3027898 A allele was detected in 67% of RA patients and 70% of controls indicating that it is not associated with RA in codominant, dominant, or recessive models even after stratification by age and gender. The miR-146a rs2910164 G allele was detected in 76% of RA patients and 68% of controls, thus the C allele confers some protection based on a dominant model [CC+GC (odds ratio (95% confidence interval) = 0.6 (0.3-0.9), p = 0.03)]. No association with CRP, RF, anti-CCP, or erosion was found for either SNPs.
The IRAK1 rs3027898 was not associated with RA, whereas C allele of miR-146a rs2910164 was found to be protective. Functional studies are required to investigate the exact role of miR-146a rs2910164 during RA.
类风湿关节炎（RA）的特征是通过活化B细胞核因子κB（NF-κB）信号通路产生一系列促炎细胞因子。白细胞介素-1受体（IL-1R）和Toll样受体含有一个共同的胞质基序，即Toll/IL-1R（TIR）同源结构域。该基序是NF-κB激活所必需的。IL-1R相关激酶1（IRAK1）是TIR信号级联过程中招募的关键衔接分子。其基因表达受微小RNA（miR）-146a调控。
我们研究了IRAK1单核苷酸多态性（SNP）rs3027898（IRAK1 rs3027898）和miR-146a SNP rs2910164（miR-146a rs2910164）在突尼斯RA患者中的作用及其与C反应蛋白（CRP）、类风湿因子（RF）、抗环瓜氨酸肽（抗CCP）抗体和侵蚀的关系。
在172例成年RA患者和224例匹配对照组成的队列中，采用新设计的引物通过诱变分离聚合酶链反应（MS-PCR）确定IRAK1 rs3027898基因分型，通过片段长度多态性PCR-限制性内切酶（RFLP-PCR）确定miR-146a rs2910164基因分型。
在67%的RA患者和70%的对照中检测到IRAK1 rs3027898 A等位基因，这表明即使按年龄和性别分层后，在共显性、显性或隐性模型中它与RA均无关联。在76%的RA患者和68%的对照中检测到miR-146a rs2910164 G等位基因，因此基于显性模型，C等位基因具有一定的保护作用[CC + GC（优势比（95%置信区间）= 0.6（0.3 - 0.9），p = 0.03）]。两种SNP均未发现与CRP、RF、抗CCP或侵蚀有关联。
IRAK1 rs3027898与RA无关，而miR-146a rs2910164 C等位基因具有保护作用。需要进行功能研究以探讨miR-146a rs2910164在RA中的确切作用。
