Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 2 2021 04 17 178 187 Naeim Ehtesham 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 Behrang Alani Department of Applied Cell Sciences, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran Deniz Mortazavi Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Sara Azhdari Department of Anatomy and Embryology, School of Medicine, Bam University of Medical Sciences, Bam, Iran Taiebe Kenarangi Student Research Committee, Faculty of Statistics, University of Social Welfare and Rehabilitation Science, Tehran, Iran Emran Esmaeilzadeh School of Medicine, AJA University of Medical Science, Tehran, Iran Bahram Pakzad Department of Internal Medicine, Division of Rheumatology, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran 2021 01 11 2021 02 27 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 3ˊUTR 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. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3094 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3094/1693