IL-17Rβ, IL-23α, IL-2R, IL-6, IL-2 and IL-18R. IL-6 activates the production of CRP (C-reactive protein) and fibrinogen through the liver and IL-17Rβ, IL-23α, IL-2R, IL-6, IL-2 and IL-18R contribute to the progress and pathogenesis of RA

Single nucleotide polymorphisms in pre-microRNA (miRNA) may alter miRNA expression levels or processing and contribute to susceptibility in a wide range of diseases. The present study aimed to evaluate the possible association between rs2910164 and rs3746444 of the pre-miRNA (hsamir-146a and hsa-mir-499) polymorphisms and susceptibility to rheumatoid arthritis (RA) in an Iranian population. This case-control study was performed on 104 patients with RA and 110 healthy individuals. Tetra amplification refractory mutation system-polymerase chain reaction was used to genotype the hsa-mir-499 rs3746444 and hsa-mir-146a rs2910164 polymorphisms. The hsa-mir-499 rs3746444 polymorphism was a risk factor for predisposition to RA in codominant [TT vs. TC: odds ratio (OR), 2.11; 95% confidence interval (CI), 1.08-4.11; P=0.029; TT vs. CC: OR, 3.88; 95% CI, 1.68-8.98; P=0.002], dominant (TT vs. TC-CC: OR, 2.64; 95% CI, 1.484.72; P=0.001) and recessive (TC-CC vs. CC: OR, 3.05; 95% CI, 1.36-6.83; P=0.007) tested inheritance models. In addition, the rs3746444 C allele was a risk factor for RA (OR, 2.49; 95% CI, 1.63-3.81; P<0.0001). No significant difference was found between the groups concerning the rs2910164 polymorphism (χ2=0.348, P=0.841). Our findings demonstrated that the hsa-mir-499 rs3746444, but not mir-146a rs2910164, polymorphism is associated with an increased RA risk in a sample of the Iranian population. Larger studies with different ethnicities are required to validate our findings. Introduction Rheumatoid arthritis (RA) is a systemic autoimmune disease which affects 0.5-1% of the general population worldwide (1). A chronic and deforming arthritis, RA is characterized by accelerated inflammatory joint destruction of articular cartilage and bone and synovial hyperplasia, which ultimately leads to severe disabilities and a poor quality of life (2,3). The etiology of RA is unknown, but genetic factors are thought to be important in the pathogenesis and progress of RA (1,4). One class of genetic variants that have recently been the center of attention are DNA polymorphisms that affect microRNA (miRNA) binding (5). miRNAs are approximately 22-nucleotide (nt) non-coding RNAs that are involved in the post-transcriptional regulation of gene expression by affecting the stability and translation of mRNAs (6). Compelling evidence indicates that miRNAs act as key regulators of various processes, including early development, cell proliferation, differentiation, stress resistance, cell fate determination, apoptosis, signal transduction and organ development (7-10). miRNAs are present in dried biological fluids, including semen, saliva, vaginal secretions and menstrual blood and are expected to be diagnostic and prognostic biomarkers of various diseases, including cancer and autoimmune diseases such as RA (11,12). Abnormal expression of several miRNAs has been detected in RA in various cell types and these miRNAs regulate specific pathways, thus leading to the inflammatory milieu occurring in RA (2). Hsa-mir-499 is involved in autoimmune and inflammatory disease. The targets of hsa-mir-499 include IL-17Rβ, IL-23α, IL-2R, IL-6, IL-2 and IL-18R. IL-6 activates the production of CRP (C-reactive protein) and fibrinogen through the liver and IL-17Rβ, IL-23α, IL-2R, IL-6, IL-2 and IL-18R contribute to the progress and pathogenesis of RA (8). Findings of recent studies have shown that the rs3746444 polymorphism in the pre-miR-499 is correlated with several diseases, including breast cancer (13), cervical squamous cell carcinoma (CSCC) (14), hepatocellular carcinoma (15), RA (8), coronary artery disease (CAD) (16), chronic obstructive pulmonary disease (COPD) (17) and tuberculosis (17). Association of pre-miRNA-146a rs2910164 and pre-miRNA-499 rs3746444 polymorphisms and susceptibility to rheumatoid arthritis MOHAMMAD HASHEMI1,2, EBRAHIM ESKANDARI-NASAB2, ZAHRA ZAKERI3, MAHDI ATABAKI4, GHOLAMREZA BAHARI2, MAHDI JAHANTIGH5, MOHSEN TAHERI6 and SAEID GHAVAMI7 1Cellular and Molecular Research Center, Zahedan University of Medical Sciences; Departments of 2Clinical Biochemistry, 3Internal Medicine, 4Immunology and 5Pathology, School of Medicine; 6Genetics of Non Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Iran; 7Department of Physiology, Manitoba Institute of Child Health, University of Manitoba, Winnipeg, MB, Canada Received July 9, 2012; Accepted October 2, 2012 DOI: 10.3892/mmr.2012.1176 Correspondence to: Professor Mohammad Hashemi, Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Khalij Fars Blv, Zahedan, Iran E-mail: [email protected]; [email protected]