Epigenetic predictor of smoking status in buccal cells

IF 3.3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicology and applied pharmacology Pub Date : 2025-05-27 DOI:10.1016/j.taap.2025.117415

Ewelina Pośpiech , Aleksandra Pisarek-Pacek , Kinga Herda , Bożena Wysocka , Aneta Sitek , Magdalena Spólnicka , Wojciech Branicki , Andrzej Ossowski

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引用次数: 0

Abstract

Smoking is the leading cause of accelerated aging and death worldwide. Therefore, identifying and intervening at smoke-responsive DNA methylation markers may be a primary way to reduce mortality risk in the population. Many studies have investigated the association between smoking and DNA methylation in blood samples. Only a few studies have examined saliva and buccal cells in this regard.

Here, we determined DNA methylation profiles in buccal cells from a total of 280 individuals. Epigenome-wide association analysis (N = 200) uncovered 61 CpG markers, including novel ones, that were significantly associated with smoke exposure in this tissue type. Functional analysis showed that they were overrepresented in the Wnt signaling pathway and fatty acid metabolism. We confirmed that AHRR, a known smoking marker in blood, is also a top locus in buccal cells. However, cg06036945 (p = 1.76 × 10^-10) and cg04066994 (p = 1.36 × 10^-6) may be more informative for smoking in buccal epithelium than the commonly reported cg05575921. Moreover, unlike in blood, several other loci with a similar effect size were discovered in our study, including DKK3 cg16859537 (p = 3.10 × 10^-10) and CYP1B1 cg02162897 (p = 5.67 × 10^-10). The CYP1B1 and AHRR genes are known to interact through the Ah receptor pathway and play an important role in oxidative stress and mediating toxicity. Finally, logistic regression was employed for variable selection and to derive a novel DNA methylation-based classifier for smoking in buccal cells. Four CpG sites, CYP1B1 cg02162897, DKK3 cg16859537, AXIN1 cg12969952 and PKN1 cg12581991 predicted tobacco use with a cross-validated AUC = 0.8, sensitivity of 65.7 % and specificity of 81.5 %. The model was further validated in an independent set of N = 80 samples.

The identified genes and pathways may serve as targets for intervention or risk stratification in respiratory diseases, while the developed models can also be instrumental in monitoring patient compliance with treatment recommendations and in behavioral profiling within forensic contexts.

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口腔细胞吸烟状态的表观遗传预测因子。

吸烟是世界范围内加速衰老和死亡的主要原因。因此，识别和干预烟雾反应性DNA甲基化标记可能是降低人群死亡风险的主要途径。许多研究调查了血液样本中吸烟和DNA甲基化之间的关系。在这方面，只有少数研究对唾液和口腔细胞进行了检查。在这里，我们确定了来自280个个体的口腔细胞的DNA甲基化谱。表观基因组关联分析（N = 200）发现61个CpG标记，包括新的标记，与该组织类型的烟雾暴露显着相关。功能分析显示，它们在Wnt信号通路和脂肪酸代谢中被过度代表。我们证实，血液中已知的吸烟标志物AHRR也是口腔细胞中的顶级位点。然而，cg06036945 （p = 1.76 × 10-10）和cg04066994 （p = 1.36 × 10-6）可能比通常报道的cg05575921更能说明吸烟对口腔上皮的影响。此外，与血液不同，在我们的研究中发现了其他几个具有类似效应大小的基因座，包括DKK3 cg16859537 （p = 3.10 × 10-10）和CYP1B1 cg02162897 （p = 5.67 × 10-10）。CYP1B1和AHRR基因通过Ah受体途径相互作用，在氧化应激和介导毒性中发挥重要作用。最后，采用逻辑回归进行变量选择，并推导出一种新的基于DNA甲基化的口腔细胞吸烟分类器。4个CpG位点CYP1B1 cg02162897、DKK3 cg16859537、AXIN1 cg12969952和PKN1 cg12581991预测烟草使用，交叉验证AUC = 0.8，敏感性为65.7% %，特异性为81.5 %。在N = 80个样本的独立集合中进一步验证模型。已确定的基因和途径可作为呼吸系统疾病干预或风险分层的目标，而开发的模型也可用于监测患者对治疗建议的遵守情况，并在法医背景下进行行为分析。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology and applied pharmacology 医学-毒理学

CiteScore

6.80

自引率

2.60%

发文量

309

审稿时长

32 days

期刊介绍： Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.