HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

miR-146a polymorphism influences levels of miR-146a, IRAK-1, and TRAF-6 in young patients with coronary artery disease.

Abstract
Modulation of nuclear factor KappaB (NF-κB) activation may play a role in regulating inflammatory conditions associated with coronary artery disease (CAD). MicroRNA-146a (miR-146a) primarily targets interleukin-1 receptor-associated kinase 1 (IRAK-1) and tumour necrosis factor receptor associated factor 6 (TRAF-6), which results in inhibition of NF-κB via the TLR pathway. This study investigated the influence of the miR-146a GC rs2910164 on miR-146a expression in young South African Indians with CAD. CAD patients and controls were genotyped by PCR-RFLP and miRNA-146a levels were measured by qPCR. IRAK-1, TRAF-6 and NF-κB expression was determined by Western blot. No differences in genotypic frequency was found (GG: 45 vs. 47%, GC: 46 vs. 41%, CC: 9 vs. 12%) in controls and patients respectively (odds ratio = 1.025; 95% confidence interval 0.6782-1.550; p = 0.9164). Significantly higher levels of miR-146a was associated with CAD patients with the CC genotype (6.25-fold increase relative to controls and patients with the wildtype variant, p < 0.0001). Significantly lower levels of IRAK-1 (0.38 ± 0.02; p = 0.0072) and TRAF-6 (0.44 ± 0.02; p = 0.0146) was found in CAD patients with the CC genotype. The lowest levels of NF-κB and C-reactive protein were found in patients with the homozygous C allele compared to the heterozygous GC and wildtype variants. We propose a role for miR-146a in TLR signalling through a negative feedback mechanism involving the attenuation of NF-κB by down-regulation of IRAK-1 and TRAF-6. Our observations implicate miR-146a as a target for lowering inflammation in CAD patients.
AuthorsPrithiksha Ramkaran, Sajidah Khan, Alisa Phulukdaree, Devapregasan Moodley, Anil A Chuturgoon
JournalCell biochemistry and biophysics (Cell Biochem Biophys) Vol. 68 Issue 2 Pg. 259-66 (Mar 2014) ISSN: 1559-0283 [Electronic] United States
PMID23794009 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • MIRN146 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • RNA, Messenger
  • TNF Receptor-Associated Factor 6
  • C-Reactive Protein
  • Interleukin-1 Receptor-Associated Kinases
Topics
  • Adult
  • Alleles
  • C-Reactive Protein (analysis)
  • Coronary Artery Disease (genetics, metabolism, pathology)
  • Down-Regulation
  • Genotype
  • Homozygote
  • Humans
  • Interleukin-1 Receptor-Associated Kinases (genetics, metabolism)
  • Male
  • MicroRNAs (genetics, metabolism)
  • NF-kappa B (genetics, metabolism)
  • Odds Ratio
  • Polymorphism, Genetic
  • RNA, Messenger (metabolism)
  • TNF Receptor-Associated Factor 6 (genetics, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: