Arif Ehtesham, Ahsan Aarif, Vibhuti Arpana, Rajput Charu, Deepak Desh, Athar Mohammad, Singh Bhawani, Pasha M A Qadar
Functional Genomics Unit, Institute of Genomics and Integrative Biology, Delhi 110 007, India.
Biochem Biophys Res Commun. 2007 Sep 14;361(1):182-8. doi: 10.1016/j.bbrc.2007.07.008. Epub 2007 Jul 16.
Nitric oxide (NO) plays critical role in endothelial dysfunction and oxidative stress in COPD, pointing to the significance of endothelial nitric oxide synthase gene (eNOS) variants. We investigated the association of -786T/C, -922A/G, 4B/4A, and 894G/T polymorphisms of eNOS with the disease and its impact on nitrite and malonaldehyde levels in 190 COPD patients and 134 healthy controls, all smokers. The -786C, -922G and 4A alleles were significantly over-represented in patients (p=0.02, p=0.02, and p=0.03, respectively). The haplotypes, -786C:4A, 4A:894G, -786C:894G, and -786C:4A:894G were significantly over-represented in patients (p<0.0001, p =0.02, p=0.02, and p <0.0001, respectively), whereas, haplotypes, -786T:4B, 4B:894G, -786T:894G, and -786T:4B:894G were significantly under-represented in the patients (p<0.0001). The patients had significantly increased levels of nitrite (p=0.003) and malonaldehyde (p<0.0001). Combination of genotypes containing -786C and 4A alleles were greater in patients (p 0.05), and these combinations associated with decreased FEV1 value and nitrite level (p=0.03 and p=0.04, respectively) and with increased malonaldehyde levels (p=0.02). The eNOS -786C, -922G, and 4A alleles, these alleles associated haplotypes and genotype combinations were over-represented in patients. The variants and their combinations of four polymorphisms of eNOS contribute to disturbed pulmonary function and oxidative stress in COPD.
一氧化氮（NO）在慢性阻塞性肺疾病（COPD）的内皮功能障碍和氧化应激中起关键作用，这表明内皮型一氧化氮合酶基因（eNOS）变异具有重要意义。我们研究了eNOS基因的-786T/C、-922A/G、4B/4A和894G/T多态性与该疾病的关联，以及它们对190例COPD患者和134例健康对照者（均为吸烟者）亚硝酸盐和丙二醛水平的影响。-786C、-922G和4A等位基因在患者中显著过度表达（分别为p=0.02、p=0.02和p=0.03）。单倍型-786C:4A、4A:894G、-786C:894G和-786C:4A:894G在患者中显著过度表达（分别为p<0.0001、p =0.02、p=0.02和p <0.0001），而单倍型-786T:4B、4B:894G、-786T:894G和-786T:4B:894G在患者中显著低表达（p<0.0001）。患者的亚硝酸盐（p=0.003）和丙二醛水平（p<0.0001）显著升高。含有-786C和4A等位基因的基因型组合在患者中更多（p 0.05），这些组合与FEV1值降低和亚硝酸盐水平降低（分别为p=0.03和p=0.04）以及丙二醛水平升高（p=0.02）相关。eNOS的-786C、-922G和4A等位基因、这些等位基因相关的单倍型和基因型组合在患者中过度表达。eNOS四个多态性的变异及其组合导致了COPD患者肺功能紊乱和氧化应激。
