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慢性阻塞性肺疾病患者血红素加氧酶-1基因启动子多态性对其基因表达的影响

The effect of polymorphism of heme oxygenase-1 gene promoter on the expression of HO-1 gene in patients with chronic obstructive pulmonary disease

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【作者】 马志明张珍祥韩泽民徐永健

【Author】 Ma Zhiming, Zhang Zhenxiang, Han Zemin, et al. Department of Respiratory Medicine, Tongji Hospital Affiliated Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030,China

【机构】 华中科技大学同济医学院附属同济医院呼吸内科华中科技大学同济医学院附属同济医院呼吸内科 (430030)现工作单位广州市胸科医院(510095)(430030)(430030)现工作单位武汉解放军457医院(430012)(430030)

【摘要】 目的:探讨COPD患者血红素加氧酶1(heme oxygenase1,HO1)基因启动子多态性对HO1基因表达水平的影响。方法:利用PCR、免疫组织化学及原位杂交等技术,在50例肺癌合并COPD组(COPD组)与30例单纯肺癌组(对照组)的肺组织中,检测HO1基因启动子5’端(GT)n重复序列不同基因型的频率分布特征,及分析其与HO1基因信使核糖核酸(messenger ribonucleic acid,mRNA)表达及HO1蛋白表达的关系。结果:①COPD组L/M基因型频率显著高于对照组,而S/S基因型频率显著低于对照组(均为P<0.05),其它基因型频率比较差异无统计学意义(均为P>0.05);②HO1基因启动子(GT)n不同重复序列含有L等位基因样本(Ⅰ组)其HO1mRNA和蛋白表达水平显著低于不含有L等位基因的Ⅱ组(均为P<0.01)。结论:HO1基因启动子5’端(GT)n大量重复序列可能降低了HO1基因的表达水平,而与COPD的易感性有关。

【Abstract】 Objective: To study the effect of polymorphism of heme oxygenase-1(HO-1)gene promoter on the expression of HO-1 gene in patients with chronic obstructive pulmonary disease(COPD)Methods: Polymerase chain reaction(PCR), immunohistochemistry and insitu hybridization were used to analyze the characteristics of the distribution of the numbers of (GT)n in HO-1 gene promoter in 50 patients with both lung cancer and COPD(COPD group)and 30 patients with lung cancer alone (control group)The relationship between the different genotypes of (GT)n repeats in the HO-1 gene promoter and the expression of messenger ribonucleic acid (mRNA) and protein of HO1 was analyzedResults:①The L/M genotypic frequency in the COPD group was significantly higher than that of the control group and the S/S genotypic frequency in the COPD was significantly lower than that of the control group(P<0.05,P<0.05) However, no statistical difference was found in other genotypic frequencies(P>0.05) ②The expression of HO-1 gene mRNA and protein in subjects with L allele in the (GT)n repeats of HO-1 gene promoter (groupⅠ) was significantly lower than that of the group Ⅱwithout L allele(P﹤0.01,P﹤0.01)Conclusions: The large size of a (GT)n repeat in the HO-1 gene promoter may reduce the expression of HO-1 gene,which may be associated with the susceptibility to COPD .

【基金】 “十五”国家科技攻关计划项目[编号2001BA703B03(B)];卫生部部属临床学科重点项目(学科代码3202060)1
  • 【分类号】R563.9
  • 【被引频次】15
  • 【下载频次】189
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