miR-146a Polymorphism Influences Levels of miR-146a,IRAK-1, and TRAF-6 in Young Patients with Coronary Artery Disease

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.     

A Sometimes-Pool Estimator of the Mean Life

The paper deals with the problem of estimating the mean life θ in an exponential model \documentclass{article}\pagestyle{empty}\begin{document}$f(x/\theta ) = \frac{1}{\theta }e - x/\theta$\end{document}. It is assumed that in addition to the current ordered sample, we have a sample collected sometime in the recent past when the mean life might have been β. We have proposed a Sometimes—Pool procedure which is based on the outcome of a preliminary test of H₀: θ=β and obtained the expressions of the bias and MSE. An attempt has been made to locate that region in the parameter space in which the proposed estimator does better (in MSE sense) than the usual estimator based only on the current sample.