Relationships of Long-Term Smoking and Moist Snuff Consumption With a DNA Methylation Age Relevant Smoking Index: An Analysis in Buccal Cells.
Relationships of Long-Term Smoking and Moist Snuff Consumption With a DNA Methylation Age Relevant Smoking Index: An Analysis in Buccal Cells.
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长期吸烟和湿鼻烟消费与 DNA 甲基化年龄相关吸烟指数的关系：颊细胞分析。
DOI：
10.1093/ntr/nty156
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Boyer,EdwardW
中科院分区：
文献类型：
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作者：
Nwanaji-Enwerem,JamajiC;Cardenas,Andres;Chai,PeterR;Weisskopf,MarcG;Baccarelli,AndreaA;Boyer,EdwardW
简介目前，还没有一种被广泛接受的、非自我报告的测量方法可以同时反映吸烟行为并在分子水平上提供一般疾病过程的信息。最近，研究人员利用有核血细胞和基于多组织 DNA 甲基化的实际年龄和疾病预测因子（DNA 甲基化年龄 [DNAm-age]）开发了吸烟指数 (SI)。为了更好地了解这种新型 SI 在易于获取的细胞类型中的效用，我们使用口腔细胞 DNA 甲基化来检查 SI 与长期吸烟和湿鼻烟消费的关系。方法我们使用了一个公开的数据集，该数据集由 120 名中年男性（40 名长期吸烟者、40 名湿鼻烟消费者和 40 名不吸烟者）的口腔细胞 DNA 甲基化值组成。 DNAm-age (353-CpGs) 和 SI (66-CpGs) 使用 Illumina HumanMmethylation450 BeadChip 测量的 CpG 位点计算。我们使用针对实际年龄、种族和甲基化技术协变量进行调整的线性回归模型估计了烟草消费习惯与 SI 和 DNAm 年龄的关联。结果在以非吸烟者为参考的完全调整模型中，吸烟（β = 1.08，95% CI = 0.82 至 1.33，p< .0001），但不吸鼻烟（β = .06，95% CI = -0.19 至0.32，p= .63）与 SI 显着相关。 SI 是吸烟与不吸烟的极好预测指标（曲线下面积 = 0.92，95% CI = 0.85 至 0.98）。四种 DNAm-age CpG 在吸烟者和非吸烟者之间存在差异甲基化，其中包括 cg14992253 [EIF3I]，此前已证明该基因会随着长期暴露于细颗粒空气污染 (PM2.5) 而发生差异甲基化。结论 66-CpG SI 似乎是测量口腔细胞吸烟特异性行为的有用工具。尽管如此，仍需要进一步的研究来广泛证实我们的发现以及 SI 与 DNAm-age 的关系。 意义我们的研究结果表明，这种 66-CpG 血液来源的 SI 可以反映口腔细胞中的长期吸烟情况，但不能反映长期吸鼻烟的情况。这一证据将非常有用，因为该领域正在努力确定一种可以在易于接近的组织中测量的准确的非自我报告吸烟生物标志物。未来的研究工作应侧重于 (1) 优化 SI 与 DNAm 年龄的关系，以便该指标能够最大限度地发挥其作为理解一般疾病过程的工具的效用，以及 (2) 确定 SI CpG 的正常值，以便该指标不具有研究样本特定性。
IntroductionCurrently, there is no widely accepted, non-self-report measure that simultaneously reflects smoking behaviors and is molecularly informative of general disease processes. Recently, researchers developed a smoking index (SI) using nucleated blood cells and a multi-tissue DNA methylation–based predictor of chronological age and disease (DNA methylation age [DNAm-age]). To better understand the utility of this novel SI in readily accessible cell types, we used buccal cell DNA methylation to examine SI relationships with long-term tobacco smoking and moist snuff consumption.MethodsWe used a publicly available dataset composed of buccal cell DNA methylation values from 120 middle-aged men (40 long-term smokers, 40 moist snuff consumers, and 40 nonsmokers). DNAm-age (353-CpGs) and SI (66-CpGs) were calculated using CpG sites measured using the Illumina HumanMethylation450 BeadChip. We estimated associations of tobacco consumption habits with both SI and DNAm-age using linear regression models adjusted for chronological age, race, and methylation technical covariates.ResultsIn fully adjusted models with nonsmokers as the reference, smoking (β = 1.08, 95% CI = 0.82 to 1.33,p< .0001) but not snuff consumption (β = .06, 95% CI = −0.19 to 0.32,p= .63) was significantly associated with SI. SI was an excellent predictor of smoking versus nonsmoking (area under the curve = 0.92, 95% CI = 0.85 to 0.98). Four DNAm-age CpGs were differentially methylated between smokers and nonsmokers including cg14992253 [EIF3I], which has been previously shown to be differentially methylated with exposure to long-term fine-particle air pollution (PM2.5).ConclusionsThe 66-CpG SI appears to be a useful tool for measuring smoking-specific behaviors in buccal cells. Still, further research is needed to broadly confirm our findings and SI relationships with DNAm-age.ImplicationsOur findings demonstrate that this 66-CpG blood-derived SI can reflect long-term tobacco smoking, but not long-term snuff consumption, in buccal cells. This evidence will be useful as the field works to identify an accurate non-self-report smoking biomarker that can be measured in an easily accessible tissue. Future research efforts should focus on (1) optimizing the relationship of the SI with DNAm-age so that the metric can maximize its utility as a tool for understanding general disease processes, and (2) determining normal values for the SI CpGs so that the measure is not as study sample specific.