國家衛生研究院 NHRI:Item 3990099045/2136
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    題名: Microsatellite polymorphism in promoter of heme oxygenase-1 gene is associated with susceptibility to coronary artery disease in type 2 diabetic patients
    作者: Chen, YH;Lin, SJ;Lin, MW;Tsai, HL;Kuo, SS;Chen, JW;Charng, MJ;Wu, TC;Chen, LC;Ding, PYA;Pan, WH;Jou, YS;Chau, LY
    貢獻者: Division of Molecular and Genomic Medicine
    摘要: Heme oxygenase is a rate-limiting enzyme in heme degradation, leading to the generation of free iron, biliverdin, and carbon monoxide. Induction of heme oxygenase-1 is implicated in the antioxidant defense mechanism and can modulate vascular function. To test the association of microsatellite polymorphism in the promoter region of human HO-1 gene with the risk of coronary artery disease (CAD) in type 2 diabetic patients, we examined the allele frequencies of (GT)(n), repeats in HO-1 gene in 474 patients with CAD and in 322 controls. A transient-transfection assay with HO-1 promoter/luciferase fusion constructs carrying various lengths of (GT), repeats was performed to explore the regulatory effect of (GT),, repeats on HO-1 gene expression in cultured rat aortic smooth muscle cells. Serum thiobarbituric acid-reactive substances (TBARs), a measure of lipid peroxidation, was significantly higher in subjects carrying the L/L genotype (greater than or equal to32 repeats). Among type 2 diabetic subjects, the frequencies of the L alleles and proportion of genotypes with L alleles were significantly higher in those with CAD than in those without CAD. The adjusted odds ratio for CAD in type 2 diabetic patients with L alleles was 4.7 (95% confidence interval, 1.9-12.0, P=0.001). Transfection experiments in aortic smooth muscle cells revealed that HO-1 promoter/luciferase fusion constructs containing longer (GT),, repeats exhibited lower transcriptional activity. These results imply that the length polymorphism in the HO-1 gene promoter modulate the transcription of the gene in vascular cells. Type 2 diabetics carrying longer (GT),, repeats might have higher oxidative stress and increased susceptibility to the development of CAD.
    關鍵詞: Genetics & Heredity
    日期: 2002-07
    關聯: Human Genetics. 2002 Jul;111(1):1-8.
    Link to: http://dx.doi.org/10.1007/s00439-002-0769-4
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0340-6717&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000177218000001
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0036664867
    顯示於類別:[周玉山(1996-2005)] 期刊論文

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