Associations of Rs3744841 and Rs3744843 Polymorphisms in Endothelial Lipase Gene with Risk of Coronary Artery Disease and Lipid Levels in a Chinese Population

<div><p>Objective</p><p>The aim of the present study was to assess the association between the 2037T/C and 2237G/A polymorphisms in the <i>EL</i> gene and the risk of CAD and lipid levels in a Chinese population.</p><p>Methods</p><p>A case-control study including 706 patients with CAD and 315 controls was performed. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to identify the genotypes.</p><p>Results</p><p>The <i>EL</i> 2037 T/C polymorphism was associated with CAD risk and HDL-C levels. No significant differences were found between the <i>EL</i> 2237 G/A genotypes and CAD risk and lipid levels in the whole population. However, carriers of the 2237 A allele had higher Apo A1 levels than those with the 2237 GG genotype and in the CAD subgroup (<i>P</i> = 0.044). The CAD cases have a significantly lower frequency of the C-G haplotypes than the controls, and the T-A haplotype was significantly more common in the CAD patients than in the controls.</p><p>Conclusions</p><p>Our study concluded that the <i>EL</i> 2037 T/C polymorphism was associated with CAD risk and HDL-C levels, and that the C allele might be a protective factor against CAD in the Chinese Han population. In addition, the <i>EL</i> 2237 A allele might be associated with an increased Apo A1 level in CAD subjects.</p></div

The Size distribution of reads generated from 454 FLX platform pyrosequencing.

<p>The Size distribution of reads generated from 454 FLX platform pyrosequencing.</p

Effect of <i>EL</i> 2237 G/A genotypes on serum lipid levels.

<p>Effect of <i>EL</i> 2237 G/A genotypes on serum lipid levels.</p

<i>Mycobacterium bovis</i> BCG Triggered MyD88 Induces miR-124 Feedback Negatively Regulates Immune Response in Alveolar Epithelial Cells

<div><p>The emerging roles of microRNAs (miRNAs) and pulmonary epithelial cells in regulating the immune response against microbial invasion has attracted increasing attention in recent years, however, the immunoregulatory roles of miRNAs in the pulmonary epithelial cells in response to mycobacterial infection has not been fully demonstrated. In this study, we show that miR-124 expression is induced upon <i>Mycobacterium bovis</i> Bacillus Calmette-Guerin (BCG) infection in A549 alveolar epithelial cells and murine lungs. miR-124 is able to modulate Toll-like receptor (TLR) signaling in A459 cells. In this regard, multiple components, including TLR6, myeloid differentiation factor 88 (MyD88), TNFR-associated factor 6 and tumor necrosis factor-α of the TLR signaling cascade are directly regulated by miR-124 in response to BCG stimulation. In addition, miR-124 expression was induced upon MyD88 overexpression and/or BCG stimulation, while silencing MyD88 expression by small interfering RNA dramatically down-regulated miR-124 transcription in A549 cells. These results indicate an underlying negative feedback mechanism between miR-124 and MyD88 in alveolar epithelial cells to prevent an excessive inflammatory response during mycobacterial infection. These observations suggest that miR-124 is a potential target for preventive and therapeutic intervention against the pulmonary tuberculosis, an infectious disease caused by <i>Mycobacterium tuberculosis</i> infection.</p></div

The size distribution of contigs resulted from de

<p>The size distribution of contigs resulted from de</p

Validation of potential targets of miR-124 by a dual-luciferase reporter assay.

<p>A: Sequences of potential binding sites of miR-124 in the 3′UTR of TLR6, MyD88, TRAF6 and TNF-α mRNA (top sequences). Mutations were introduced into the putative miR-124 binding sites to generate variant 3′UTRs (bottom sequence). B-E: Dual-luciferase reporter assays were designed to validate miR-124 specificity. Cells were transfected with miR-124 mimic, miR-124 inhibitor or miR-124 control and pMIR-Report/TLR6 containing wild type or mutant 3′UTR sequence (B), pMIR-Report/MyD88 containing wild type or mutant 3′UTR sequence (C), pMIR-Report/TRAF6 containing wild type or mutant 3′UTR sequence (D) or pMIR-Report/TNF-α containing wild type or mutant 3′UTR sequence (E). Compared with pSicoR/nc group, *: p<0.05. Results represent the mean ± SD from three independent triplicated experiments (N = 9).</p

Summary of contigs generated by de

<p>Summary of contigs generated by de</p

The classification of unigenes in three GO categories (level 3).

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102668#pone-0102668-g003" target="_blank">Figure 3</a>–1 indicated biological process; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102668#pone-0102668-g003" target="_blank">Figure 3</a>–2 indicated cellular component; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102668#pone-0102668-g003" target="_blank">Figure 3–3</a> indicated molecular function; The x-axis indicated the number of unigenes in a process; The y-axis indicated GO process.</p

The ten most representive pathways resulted from KEGG pathway annotation.

<p>The x-axis indicated the number of unigenes in a pathway; The y-axis indicated the ten representive pathway.</p

miR-124 targets TLR6 mRNA.

<p>TLR6 mRNA and protein was detected by a qRT-PCR (top panels) or an immunoblotting assay (bottom panels), respectively in naïve A549 cells (A) or cells infected with BCG (B). A549 cells were transfected with pcDNA3.1, miR-124 nc, miR-124 mimic or miR-124 inhibitor, followed by BCG infection. Comparisons were made to cells transfected with pcDNA3.1, *: p<0.05. Data represented the mean ± SD from three independent triplicated experiments (N = 9).</p