title: Micro RNA-146a But Not IRAK1 is Associated with Rheumatoid Arthritis in the Tunisian Population.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1 Laboratory of Immunology , Research Unit UR 807, Faculty of Medicine of Sousse, Sousse, Tunisia .
authors.forename: Hana Ben
authors.initials: HB
authors.lastname: Hassine
authors.affiliation: 1 Laboratory of Immunology , Research Unit UR 807, Faculty of Medicine of Sousse, Sousse, Tunisia .
authors.forename: Asma
authors.initials: A
authors.lastname: Boumiza
authors.affiliation: 1 Laboratory of Immunology , Research Unit UR 807, Faculty of Medicine of Sousse, Sousse, Tunisia .
authors.forename: Rim
authors.initials: R
authors.lastname: Sghiri
authors.affiliation: 2 Department of Rheumatology, Farhat Hached Hospital , Sousse, Tunisia .
authors.forename: Khadija
authors.initials: K
authors.lastname: Baccouche
authors.affiliation: 1 Laboratory of Immunology , Research Unit UR 807, Faculty of Medicine of Sousse, Sousse, Tunisia .
authors.forename: Imen
authors.initials: I
authors.lastname: Boussaid
authors.affiliation: 1 Laboratory of Immunology , Research Unit UR 807, Faculty of Medicine of Sousse, Sousse, Tunisia .
authors.forename: Ahlem
authors.initials: A
authors.lastname: Atig
authors.affiliation: 3 Laboratory of Immunology, King Khalid Hospital , Riyadh, Saudi Arabia .
authors.forename: Zahid
authors.initials: Z
authors.lastname: Shakoor
authors.affiliation: 2 Department of Rheumatology, Farhat Hached Hospital , Sousse, Tunisia .
authors.forename: Elyes
authors.initials: E
authors.lastname: Bouajina
authors.affiliation: 1 Laboratory of Immunology , Research Unit UR 807, Faculty of Medicine of Sousse, Sousse, Tunisia .
authors.forename: Ramzi
authors.initials: R
authors.lastname: Zemni
mesh_terms: D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000097:blood / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012217:Rheumatoid Factor / Q000378:metabolism; D014416:Tunisia / Q000453:epidemiology
chemical_list: C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D002097:C-Reactive Protein; D012217:Rheumatoid Factor; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases
keywords: IRAK1; miR-146a; rheumatoid arthritis; rs2910164; rs3027898