Yucesoy B, Johnson V J, Kashon M L, Fluharty K, Vallyathan V, Luster M I
Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, West Virginia 26505-2888, USA.
Thorax. 2005 Jun;60(6):492-5. doi: 10.1136/thx.2004.029090.
Oxidative stress plays a major role in the pathogenesis of interstitial lung diseases. The antioxidant enzymes glutathione S-transferases (GST) and manganese superoxide dismutase (MnSOD) are important components of lung defence against oxidative stress, and polymorphisms in the genes which regulate their expression may represent important disease modifiers.
A matched case-control study was conducted to determine the influence of the GSTP1, GSTT1 and MnSOD polymorphisms on susceptibility to progressive massive fibrosis (PMF). Seven hundred ex-coal miners were included in the study; 350 were classified as PMF cases while 350 with a similar underground mining tenure but no clinical or histological evidence of lung disease served as controls. Genotype analysis was performed on genomic DNA, using a 5' nuclease PCR assay.
None of the individual investigated polymorphisms and two-way gene-gene interactions had a statistically significant association with PMF.
The results of this study suggest that polymorphic genotypes within the GST gene cluster and MnSOD do not affect individual susceptibility to PMF.
氧化应激在间质性肺疾病的发病机制中起主要作用。抗氧化酶谷胱甘肽S-转移酶(GST)和锰超氧化物歧化酶(MnSOD)是肺部抵御氧化应激的重要组成部分,调节其表达的基因多态性可能是重要的疾病修饰因子。
进行了一项匹配病例对照研究,以确定GSTP1、GSTT1和MnSOD基因多态性对进行性大块纤维化(PMF)易感性的影响。该研究纳入了700名 former coal miners;350例被归类为PMF病例,另外350例具有相似的地下采矿年限但无肺部疾病临床或组织学证据的矿工作为对照。使用5'核酸酶PCR分析法对基因组DNA进行基因型分析。
所研究的单个多态性和双向基因-基因相互作用均与PMF无统计学显著关联。
本研究结果表明,GST基因簇和MnSOD内的多态基因型不影响个体对PMF的易感性。