A NOD2 gene polymorphism is associated with the prevalence and severity of chronic obstructive pulmonary disease in a Japanese population
A NOD2 gene polymorphism is associated with the prevalence and severity of chronic obstructive pulmonary disease in a Japanese population
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DOI：
10.1111/j.1440-1843.2011.02069.x
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发表时间：
2012-01-01
期刊：
影响因子：
6.9
通讯作者：
Mishima, Michiaki
中科院分区：
文献类型：
--
作者：
Kinose, Daisuke;Ogawa, Emiko;Mishima, Michiaki
背景与目的：遗传背景被认为是COPD发病的危险因素之一。最近，已经提出先天免疫系统参与COPD的病理生理学。我们假设核苷酸结合和寡聚化结构域（NOD）1和NOD 2基因多态性与COPD的发病机制有关。此外，这些单核苷酸多态性（SNPs）和COPD的表型之间的关联进行了analysed.Methods：日本COPD患者（n = 228）和非COPD吸烟者（n = 101）被招募从门诊在京都大学医院，京都，日本。在进入研究时，采集血液样本并进行肺功能检查。对NOD 1的6个选择的标签SNP和NOD 2的5个标签SNP进行基因分型。进一步研究与COPD相关的SNP，包括基线基因表达，全血中剪接变异体的相对比例，对配体的反应和促炎细胞因子刺激的外周血中性粒细胞中基因表达的增强。在COPD患者中，该SNP还与较低的FEV1%预测值（TT为57.2 +/- 1.8 vs TA/AA为50.8 +/- 2.3，P = 0.03）和DLCO/VA（TT为2.89 +/- 0.1 vs TA/AA为2.53 +/- 0.14，P = 0.036）相关。10 ng/mL肿瘤坏死因子-α刺激4 h后，TA/AA基因型外周血中性粒细胞NOD 2基因表达较TT基因型增加（P = 0.015）。结论：NOD 2 rs 1077861 SNP可能影响日本受试者COPD的发生和进展。
Background and objective: Genetic background is thought to be one of the risk factors for development of COPD. Recently, it has been proposed that the innate immune system is involved in the pathophysiology of COPD. We hypothesized that polymorphisms in the nucleotide-binding and oligomerization domain (NOD)1 and NOD2 genes would be associated with the pathogenesis of COPD. In addition, the associations between these single nucleotide polymorphisms (SNPs) and phenotypes of COPD were analysed.Methods: Japanese COPD patients (n = 228) and non-COPD smokers (n = 101) were recruited from the outpatient clinic at Kyoto University Hospital, Kyoto, Japan. At entry into the study, a blood sample was taken and a pulmonary function test was performed. Genotyping was performed for 6 selected tag SNPs of NOD1 and 5 tag SNPs of NOD2. Further investigations were performed for SNP that were associated with COPD, including baseline gene expression, the relative proportions of splicing variants in whole blood, responses to ligand and enhancement of gene expression in peripheral blood neutrophils stimulated with proinflammatory cytokines.Results: The distribution of NOD2 rs1077861 genotypes differed between Japanese COPD patients and non-COPD smokers (P = 0.036). This SNP was also associated with a lower FEV1 % predicted (57.2 +/- 1.8 for TT vs 50.8 +/- 2.3 for TA/AA, P = 0.03) and DLCO/VA (2.89 +/- 0.1 in TT vs 2.53 +/- 0.14 in TA/AA, P = 0.036) in COPD patients. NOD2 gene expression after stimulation with 10 ng/mL of tumour necrosis factor-a for 4 h, was increased to a greater extent in TA/AA genotype than in TT genotype peripheral blood neutrophils (P = 0.015).Conclusions: The NOD2 rs1077861 SNP may influence the development and progression of COPD in Japanese subjects.