Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran AND Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Applied Cell Sciences, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
Iran J Allergy Asthma Immunol. 2021 Apr 17;20(2):178-187.
The nucleotide-binding oligomerization domain 2 (NOD2) is the key regulator of inflammatory responses and has been involved in the pathogenesis of rheumatoid arthritis (RA). Laboratory and in silico evaluations have demonstrated that some polymorphisms in 3'UTR of NOD2 gene could influence the secondary structure of this region and similarly thermodynamic features of hybridization site and finally deregulate the expression of NOD2. In the current study, for the first time, we evaluated the possible association between single nucleotide polymorphisms (SNPs) rs3135500 and rs3135499 in the NOD2 gene with RA risk in the Iranian population. One hundred and fifteen patients with RA and 120 healthy subjects were recruited in this case-control study. Genotyping of rs3135500 and rs3135499 polymorphisms were accomplished using the real‑time polymerase chain reaction high resolution melting (HRM) method. We found a substantial association of AA and AG genotypes in rs3135500 with the risk of RA (AA vs GG; OR=5.547; 95%CI [2.564-11.999]; p<0.001 and AG vs GG; OR=2.179; 95%CI [1.145-4.147]; p=0.017). Moreover, in the patient group, there was a significant relationship between the increased concentration of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) with rs3135500 (A allele) (p<0.05). However, there were no important associations between rs3135499 with the risk of RA (p>0.05). However, we found a noteworthy association of the C allele in rs3135499 with an increased level of CRP in patients (p>0.05). Our findings propose a considerable association between NOD2 polymorphisms with increased risk of RA and disease activity.
核苷酸结合寡聚化结构域 2（NOD2）是炎症反应的关键调节因子，并且与类风湿关节炎（RA）的发病机制有关。实验室和计算机模拟评估表明，NOD2 基因 3'UTR 中的一些多态性可能会影响该区域的二级结构以及杂交位点的热力学特征，最终导致 NOD2 的表达失调。在本研究中，我们首次评估了 NOD2 基因中的单核苷酸多态性（SNP）rs3135500 和 rs3135499 与伊朗人群中 RA 风险之间的可能关联。在这项病例对照研究中，共招募了 115 名 RA 患者和 120 名健康对照者。使用实时聚合酶链反应高分辨率熔解（HRM）方法对 rs3135500 和 rs3135499 多态性进行基因分型。我们发现 rs3135500 中的 AA 和 AG 基因型与 RA 风险显著相关（AA 与 GG；OR=5.547；95%CI [2.564-11.999]；p<0.001和 AG 与 GG；OR=2.179；95%CI [1.145-4.147]；p=0.017）。此外，在患者组中，红细胞沉降率（ESR）和 C 反应蛋白（CRP）浓度的升高与 rs3135500（A 等位基因）之间存在显著关系（p<0.05）。然而，rs3135499 与 RA 风险之间没有重要关联（p>0.05）。然而，我们发现 rs3135499 中的 C 等位基因与患者 CRP 水平升高之间存在显著关联（p>0.05）。我们的研究结果表明，NOD2 多态性与 RA 风险增加和疾病活动度增加之间存在显著关联。
