title: Short (GT)                      (                         n                                ) repeats in heme oxygenase-1 gene promoter are associated with lower risk of coronary heart disease in subjects with high levels of oxidative stress.
abstract: Although (GT)                         (                            n                         ) repeats in heme oxygenase-1 (HO-1) promoter may modulate gene transcriptional activity, the association between (GT)                         (                            n                         ) repeats polymorphism and risk of coronary heart disease (CHD) from different levels of oxidative stress (OS) is unknown. We determined the allelic frequencies of (GT)                         (                            n                         ) repeats in the HO-1 gene promoter and plasma malonaldehyde (MDA) as biomarkers of OS in 2,298 pairs of CHD patients and controls in the Chinese population. Furthermore, we measured MDA in culture mediums and HO-1 expressions levels in cell lysates of endothelial cells carrying various (GT)                         (                            n                         ) genotypes under different concentrations of H(2)O(2). Compared with L/L genotype (>25 repeats) carriers, the adjusted odd ratios for S/S genotype (≤25 repeats) in subjects with different levels of OS (MDA < 1.83, 1.83-2.91, >2.91 μmol/L) were 1.06 (95%CI, 0.75 to 1.49), 0.79 (95%CI, 0.55 to 1.12), and 0.60 (95%CI, 0.44 to 0.81), respectively (P                         (interaction) = 0.002). In biological experiments, compared with endothelial cells carrying L/L genotype, cells with S/S genotype did not have a significantly higher HO-1 expression under 0 μmol/L H(2)O(2), but displayed a significantly higher HO-1 expression under 50 μmol/L H(2)O(2) (P                         (interaction) = 0.003). S/S genotype in HO-1 gene promoter is associated with a lower risk of CHD in subjects with higher levels of OS, because under conditions of high OS, the S/S genotype has higher levels of HO-1, an antioxidant.
authors: Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors: Mu
authors: M
authors: Chen
authors: Li
authors: L
authors: Zhou
authors: Hu
authors: H
authors: Ding
authors: Suli
authors: S
authors: Huang
authors: Meian
authors: M
authors: He
authors: Xiaomin
authors: X
authors: Zhang
authors: Longxian
authors: L
authors: Cheng
authors: Daowen
authors: D
authors: Wang
authors: Frank B
authors: FB
authors: Hu
authors: Tangchun
authors: T
authors: Wu
mesh_terms: D000368:Aged; D003324:Coronary Artery Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D016017:Odds Ratio; D018384:Oxidative Stress / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D020080:Tandem Repeat Sequences
chemical_list: D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1