Genetic and Functional Sequence Variants of the SIRT3 Gene Promoter in Myocardial Infarction.

Coronary artery disease (CAD), including myocardial infarction (MI), is a common complex disease that is caused by atherosclerosis. Although a large number of genetic variants have been associated with CAD, only 10% of CAD cases could be explained. It has been proposed that low frequent and rare genetic variants may be main causes for CAD. SIRT3, a mitochondrial deacetylase, plays important roles in mitochondrial function and metabolism. Lack of SIRT3 in experimental animal leads to several age-related diseases, including cardiovascular diseases. Therefore, SIRT3 gene variants may contribute to the MI development. In this study, SIRT3 gene promoter was genetically and functionally analyzed in large cohorts of MI patients (n = 319) and ethnic-matched controls (n = 322). Total twenty-three DNA sequence variants (DSVs) were identified, including 10 single-nucleotide polymorphisms (SNPs). Six novel heterozygous DSVs, g.237307A>G, g.237270G>A, g.237023_25del, g.236653C>A, g.236628G>C, g.236557T>C, and two SNPs g.237030C>T (rs12293349) and g.237022C>G (rs369344513), were identified in nine MI patients, but in none of controls. Three SNPs, g.236473C>T (rs11246029), g.236380_81ins (rs71019893) and g.236370C>G (rs185277566), were more significantly frequent in MI patients than controls (PC, significantly decreased the transcriptional activity of the SIRT3 gene promoter in cultured HEK-293 cells and H9c2 cells. Therefore, these DSVs identified in MI patients may change SIRT3 level by affecting the transcriptional activity of SIRT3 gene promoter, contributing to the MI development as a risk factor

PCR primers for the SIRT3 gene promoter.

<p>PCR primers for the SIRT3 gene promoter.</p

Relative transcriptional activities of wild type and variant SIRT3 gene promoters in H9c2 cells.

<p>Wild type and variant SIRT3 gene promoters were cloned into reporter gene vector pGL3 and transfected into H9c2 cells. Dual-luciferase activities were assayed and relative activities of SIRT3 gene promoters were obtained. Transcriptional activity of the wild type SIRT3 gene promoter was designed as 100%. Lanes 1, pGL3-WT; 2, pGL3 control; 3, pGL3-g.237312T>C (rs3817629); 4, pGL3-g.237307A>G; 5, pGL3-g.237270G>A + g.236370C>G + g.236380_81ins; 6, pGL3-g.237030C>T (rs12293349); 7, pGL3-g.237023_25del; 8, pGL3-g.237022C>G (rs369344513); 9, pGL3-g.236956G>T; 10, pGL3-g.236878_79Ins; 11, pGL3-g.236775del (rs369178836); 12, pGL3-g.236653C>A + g.236473C>T; 13, pGL3-g.236634C>T; 14, pGL3-g.236628G>C; 15, pGL3-g.236583A>C; 16, pGL3-g.236557T>C; 17, pGL3-g.236460T>C. *, P<0.05; **, P<0.01.</p

Chromatograms of the novel DSVs within the SIRT3 gene promoter identified in MI patients.

<p>All the DSVs are shown in forward orientations. For DSVs g.237307A>G, g.237270G>A, g.236653C>A, g.236628G>C and g.236557T>C, top panels show wild type and bottom panels heterozygous DSVs, which are marked with arrows. For the deletion DSV g.237023_25del, top panel shows wild type, middle panel heterozygous and bottom panel cloning DNA sequences. The deletion is underlined and labeled.</p

Locations of the DSVs within the SIRT3 gene promoter in MI patients and controls.

<p>The numbers represents the genomic DNA sequences of the human SIRT3 gene (Genebank accession number NC_000011.10). The transcription start site is at the position of 236362 in the first exon.</p

Chromatograms of the DSVs within the SIRT3 gene promoter only identified in controls.

<p>All the novel DSVs are depicted in forward orientations. The DSVs g.236956G>T, g.236634C>T, g.236583A>C, g.236460T>C and g.236458G>A, top panels show wild type and bottom panels heterozygous DSVs, which are marked with arrows. For the insertion DSV g.236878_79ins, top panel shows wild type, middle panel heterozygous and bottom panel cloning DNA sequences. The insertion is underlined and labeled.</p

The DSVs within the SIRT3 gene promoter in MI patients and controls.

<p>The DSVs within the SIRT3 gene promoter in MI patients and controls.</p

Research and Development of Electrostatic Accelerometers for Space Science Missions at HUST

High-precision electrostatic accelerometers have achieved remarkable success in satellite Earth gravity field recovery missions. Ultralow-noise inertial sensors play important roles in space gravitational wave detection missions such as the Laser Interferometer Space Antenna (LISA) mission, and key technologies have been verified in the LISA Pathfinder mission. Meanwhile, at Huazhong University of Science and Technology (HUST, China), a space accelerometer and inertial sensor based on capacitive sensors and the electrostatic control technique have also been studied and developed independently for more than 16 years. In this paper, we review the operational principle, application, and requirements of the electrostatic accelerometer and inertial sensor in different space missions. The development and progress of a space electrostatic accelerometer at HUST, including ground investigation and space verification are presented