Coronary artery disease (CAD) causes more than 700,000 deaths each year in China. Previous genome-wide association studies (GWAS) in populations of European ancestry identified several genetic loci for CAD, but no such study has yet been reported in the Chinese population. Here we report a three-stage GWAS in the Chinese Han population. We identified a new association between rs6903956 in a putative gene denoted as C6orf105 on chromosome 6p24.1 and CAD (P = 5.00 × 10⁻³, stage 2 validation; P = 3.00 × 10⁻³, P = 1.19 × 10⁻⁸ and P = 4.00 × 10⁻³ in three independent stage 3 replication populations; P = 4.87 × 10⁻¹², odds ratio = 1.51 in the combined population). The minor risk allele A of rs6903956 is associated with decreased C6orf105 mRNA expression. We report the first GWAS for CAD in the Chinese Han population and identify a SNP, rs6903956, in C6orf105 associated with susceptibility to CAD in this population.
Reactive oxygen species formed within the mammalian cell can produce 8-oxo-7,8-dihydroguanine (8-oxoG) in mRNA, which can cause base mispairing during gene expression. Here we found that administration of 8-oxoGTP in MTH1-knockdown cells results in increased 8-oxoG content in mRNA. Under this condition, an amber mutation of the reporter luciferase is suppressed. Using second-generation sequencing techniques, we found that U-to-G changes at preassigned sites of the luciferase transcript increased when 8-oxoGTP was supplied. In addition, an increased level of 8-oxoG content in RNA induced the accumulation of aggregable amyloid β peptides in cells expressing amyloid precursor protein. Our findings indicate that 8-oxoG accumulation in mRNA can alter protein synthesis in mammalian cells. Further work is required to assess the significance of these findings under normal physiological conditions.
Seepage erosion is one of the main reasons for the local collapse or instability of embankments. To investigate the characteristics and mechanism of seepage erosion for cohesionless soils, the model tests by using an independently developed seepage erosion device and the numerical simulations based on the Discrete Element Method-Computational Fluid Dynamics (DEM-CFD) coupling model were carried out. The results show that the seepage erosion process of the cohesionless soil can be characterized by four stages: stable seepage stage, fine particles upward migration stage, sand samples boiling stage, and erosion damage stage. The skeleton structure of soil sample under seepage flow is continually changed due to the loss of fine soil particles, which results in a significant decrease in the sample strength and may ultimately lead to the failure of the sample. The results of this study can provide references and bases for the design, construction, and long-term service of embankments or earth dams under the complex seepage condition, reducing the risk of seepage erosion.
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