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.
|
Authors | Prithiksha Ramkaran, Sajidah Khan, Alisa Phulukdaree, Devapregasan Moodley, Anil A Chuturgoon |
Journal | Cell biochemistry and biophysics
(Cell Biochem Biophys)
Vol. 68
Issue 2
Pg. 259-66
(Mar 2014)
ISSN: 1559-0283 [Electronic] United States |
PMID | 23794009
(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)
|