给编辑:
在最近的问题欧洲呼吸杂志田中等。1在肿瘤坏死因子(TNF)和淋巴细胞毒素甲基因研究的多态性相对于它们对吸烟者的肺功能和失败的效果找到与慢性阻塞性肺疾病(COPD)的表型的任何关联。田中等。1承认,他们的工作是不是真正的病例对照研究,但是,这将是更好地描述为对疾病严重程度的遗传贡献的调查。已经有变化的一些研究在TNF相对于易患慢性阻塞性肺病,尽管其中许多已经使用相对较小的样本大小,因此动力不足,因此有可能导致无法复制的结果。
As part of a European Union collaborative project, we have studied polymorphisms within the TNF gene in a large collection of well-characterised Caucasian COPD patients (n = 1,018) and control subjects (n = 911). COPD cases and control subjects were recruited from six European centres, as previously reported2。每个组的特征总结如下,表示为平均值±数据SD, 在适当情况下。控制:63.5%男性;age 60.8±8.9 yrs; smoking history 38.6±17.4 pack-yrs; forced expiratory volume in one second (FEV1)95.3±10.9%的预测;FEV1/用力肺活量(FVC)77.9±4.9%。例COPD患者:69.6%为男性;age 65.8±8.2 yrs; smoking history 48.9±23.6 pack-yrs; FEV143.0±15.3%预解码值;FEV1/ FVC 47.5±12.2%。
Six single nucleotide polymorphisms (SNPs) in TNF (table 1⇓)使用Taqman?的探头(Geneservice有限公司,Babraham,UK)基因分型。引物和探针序列是根据要求提供。作为用于基因分型的质量控制措施,已知基因型的样品的2%被纳入和样品的10%存在于重复检查一致性。所有的SNP均处于Hardy-Weinberg平衡。
单一的SNP与COPD的关联进行了使用卡方分析;没有SNP的显示在病例和对照(p≥0.331)之间基因型频率的显著差异。在病例和对照线性回归分析来鉴定TNF基因型对FEV任何可能的影响1(与年龄,吸烟史和性别作为协变量)。Using a stringent cut-off, this also failed to find any significant effect, with the lowest p-value being obtained for rs1800628 in controls only p = 0.010. Allowing for multiple testing, this is unlikely to be a true association.
TNF的单倍型的病例对照分析是根据进行3。Haplotypes of the TNF SNPs are shown in table 2⇓。该分析总共10种单倍型,其中7个是存在于频率> 2%鉴定。There was no significant difference in the frequency of these haplotypes between COPD cases and controls (global score statistic = 2.024, 7 degrees of freedom; p = 0.959). Similarly, using the omnibus test performed over all haplotypes in the SAS procedure PROC HAPLOTYPE [4], none of the possible subsets of the six SNPs showed a significant relationship with COPD.
在使用良好表征的COPD患者和对照这种大规模病例对照研究中,我们没有找到与COPD的发展TNF多态性的任何关联。这是与高加索人种其他较小的研究一致五-8虽然许多研究只考虑了-308 SNP。一项研究中,使用169名高加索COPD患者和358度的控制,显示出与1.9相关联的比值比的增加COPD患者489_GA基因型的9;然而,这是不是在目前的研究中复制,这表明它可能是一个假阳性结果。
For allele frequencies ranging 0.05–0.20 (using a dominant model and α = 0.01), the current study has >80% power to detect minimum effect sizes of 1.4–1.65. The fact that we see no association with any of the tumour necrosis factor single nucleotide polymorphisms or haplotypes makes it highly unlikely that polymorphisms in this gene play a major role in the susceptibility to chronic obstructive pulmonary disease.
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