The relationship of smoking to cg05575921 methylation in blood and saliva DNA samples from several studies.

The relationship of smoking to cg05575921 methylation in blood and saliva DNA samples from several studies.
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DOI:
10.1038/s41598-021-01088-7
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发表时间:
2021-11-03
期刊:
影响因子:
4.6
通讯作者:
Philibert R
Philibert R
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Dawes K;Andersen A;Reimer R;Mills JA;Hoffman E;Long JD;Miller S;Philibert R

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大量研究表明,吸烟会导致cg05575921甲基化降低。然而,除方法学问题外,该反应的幅度和剂量依赖性尚不清楚。这种不确定性是临床上使用DNA甲基化来评估和监测吸烟状况的障碍。为了更好地定义这一关系,我们对来自421名吸烟者和423名经生化证实的非吸烟者的样本进行了甲基化敏感PCR数字(MSdPCR)分析,评估了全血和/或唾液DNA中cg05575921甲基化与吸烟的关系。我们发现cg05575921甲基化表现出曲线剂量依赖性的减少,以响应香烟消费量的增加。在全血DNA中,cg05575921甲基化预测每日吸烟状况的受试者工作特征(ROC)曲线下面积(AUC)为0.98。在唾液DNA中,毛AUC为0.91,校正细胞异质性后将AUC提高到0.94。甲基化状态与Fagerstrom尼古丁依赖测试得分显著相关,但存在显著的样本异质性。我们得出结论,MSdPCR评估cg05575921甲基化是一种潜在的强大的、临床可实施的吸烟评估和管理工具。
Numerous studies have shown that cg05575921 methylation decreases in response to smoking. However, secondary to methodological issues, the magnitude and dose dependency of that response is as of yet unclear. This lack of certainty is a barrier to the use of DNA methylation clinically to assess and monitor smoking status. To better define this relationship, we conducted a joint analysis of methylation sensitive PCR digital (MSdPCR) assessments of cg05575921 methylation in whole blood and/or saliva DNA to smoking using samples from 421 smokers and 423 biochemically confirmed non-smokers from 4 previously published studies. We found that cg05575921 methylation manifested a curvilinear dose dependent decrease in response to increasing cigarette consumption. In whole blood DNA, the Receiver Operating Characteristic (ROC) Area Under the Curve (AUC) of cg05575921 methylation for predicting daily smoking status was 0.98. In saliva DNA, the gross AUC was 0.91 with correction for cellular heterogeneity improving the AUC to 0.94. Methylation status was significantly associated with the Fagerstrom Test for Nicotine Dependence score, but with significant sampling heterogeneity. We conclude that MSdPCR assessments of cg05575921 methylation are a potentially powerful, clinically implementable tool for the assessment and management of smoking.
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