Department of Genetics, Southwest Foundation for Biomedical Research, PO Box 760549, San Antonio, TX, USA.
BMC Med Genomics. 2010 Jul 15;3:29. doi: 10.1186/1755-8794-3-29.
This investigation offers insights into system-wide pathological processes induced in response to cigarette smoke exposure by determining its influences at the gene expression level.
We obtained genome-wide quantitative transcriptional profiles from 1,240 individuals from the San Antonio Family Heart Study, including 297 current smokers. Using lymphocyte samples, we identified 20,413 transcripts with significantly detectable expression levels, including both known and predicted genes. Correlation between smoking and gene expression levels was determined using a regression model that allows for residual genetic effects.
With a conservative false-discovery rate of 5% we identified 323 unique genes (342 transcripts) whose expression levels were significantly correlated with smoking behavior. These genes showed significant over-representation within a range of functional categories that correspond well with known smoking-related pathologies, including immune response, cell death, cancer, natural killer cell signaling and xenobiotic metabolism.
Our results indicate that not only individual genes but entire networks of gene interaction are influenced by cigarette smoking. This is the largest in vivo transcriptomic epidemiological study of smoking to date and reveals the significant and comprehensive influence of cigarette smoke, as an environmental variable, on the expression of genes. The central importance of this manuscript is to provide a summary of the relationships between gene expression and smoking in this exceptionally large cross-sectional data set.
本研究通过确定香烟暴露引起的全系统病理过程在基因表达水平上的影响，深入了解这些过程。
我们从圣安东尼奥家族心脏研究中的 1240 个人中获得了全基因组定量转录谱，其中包括 297 名现吸烟者。我们使用淋巴细胞样本，鉴定出了 20413 个具有明显可检测表达水平的转录本，包括已知和预测的基因。使用允许残留遗传效应的回归模型确定吸烟与基因表达水平之间的相关性。
在 5%的保守错误发现率下，我们鉴定出了 323 个独特的基因（342 个转录本），它们的表达水平与吸烟行为显著相关。这些基因在一系列功能类别中表现出显著的过度表达，这些类别与已知的与吸烟相关的病理学密切相关，包括免疫反应、细胞死亡、癌症、自然杀伤细胞信号和外来化合物代谢。
我们的研究结果表明，不仅是单个基因，而且是整个基因相互作用网络都受到香烟的影响。这是迄今为止最大的关于吸烟的体内转录组流行病学研究，揭示了香烟作为环境变量对基因表达的显著和全面影响。本研究的核心重要性在于提供了在这个非常大的横断面数据集中心因表达与吸烟之间关系的总结。
