Tehran University of Medical Sciences Iranian Journal of Public Health 2251-6085 49 4 2020 04 01 782 790 EN Kolsoum AHMADI Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran Azam SOLEIMANI Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Shadi SOLEIMANI MOTLAGH Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran Shahram BAHARVAND AHMADI Department of Internal Medicine, Artesh University of Medical Sciences, Tehran, Iran Mohammad ALMASIAN School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran Ali Asghar KIANI Department of Hematology and Blood Transfusion, School of Allied Medical Sciences, Lorestan University of Medical Sciences, Khorramabad, Iran 2018 04 30 2018 10 08 Background: The present research is a case-control study to analyze the influence of pre-miRNA-146a rs2910164 and pre‑miRNA-499 rs3746444 polymorphisms as candidate susceptibility factors for both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Methods: Polymorphism in miR146 and miR499 using ARMS-PCR was genotyped on 139 autoimmune disease (AD) patients (89 RA and 50 SLE) referred to Educational Hospitals of Khorramabad, Lorestan Province, west of Iran in 2018–2019 and 237 healthy control subjects. Results: A significant increase in the likelihood of carrying the GC vs. GG of pre-miR146-rs2910164 and T vs C allele of pre-miR499- rs3746444 in patients with RA was found. On the contrary, patients with RA were less likely to carry the TC + CC vs TT genotype and the C vs T allele of pre-miR499- rs374644. In females with the GC vs GG and GC+ CC vs GG genotypes, a significant association was found with the increased risk of RA. Interestingly, the genotypic combination of TC of the pre-miR499-rs374644 with GG of pre-miR146-rs2910164 more strongly decreased the risk of RA. In patients with SLE, no notable associations were found between both pre-miRNA-146a rs2910164 and pre‑miRNA-499 rs3746444 with risk of disease. Conclusion: Genetic polymorphisms of miR146 rs2910164 is associated with RA susceptibility especially in females. Interestingly, there is a potential in miR499 to reduce the risk with the protective effect of gene-gene interactions on miR146 in RA disease. https://ijph.tums.ac.ir/index.php/ijph/article/view/13240 https://ijph.tums.ac.ir/index.php/ijph/article/download/13240/6892