The initiation of adolescent smoking is difficult to detect using carbon monoxide or cotinine assays. Previously, we and others have shown that the methylation of cg05575921 is an accurate predictor of adult smoking status. But the dose and time dependency of the demethylation response to smoking initiation in adolescents is not yet well understood. To this end, we conducted three consecutive annual in-person interviews and biological samplings of 448 high school students (wave 1 (W1)-wave 3 (W3)). At W1 (n = 448), 62 subjects reported using tobacco and 72 subjects reported using cannabis at least once in their life-time with 38 and 20 subjects having a positive cotinine and cannabinoid levels, respectively, at W1 intake. At W3 (n = 383), 67 subjects reported using tobacco and 60 subjects reported using cannabis at least once with 75 and 60 subjects having positive cotinine and cannabinoid levels, respectively, at W3. Subjects with undetectable cotinine levels at all three-time waves had stable levels of cg05575921 methylation throughout the study (88.7% at W1 and 88.8% at W3, n = 149), while subjects with positive cotinine levels at all 3 time points manifested a steady decrease in cg05575921 methylation (81.8% at W1 and 71.3% at the W3, n = 12). In those subjects with an affirmative smoking self-report at W3 (n = 17), the amount of demethylation at cg05575921 was correlated with time and intensity of smoking. We conclude that cg05575921 methylation is a sensitive, dose-dependent indicator of early stages of smoking, and may help to identify smokers in the early stages of smoking.

中文翻译：

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初生吸烟中 cg05575921 去甲基化反应的细化。


使用一氧化碳或可替宁检测很难检测到青少年是否开始吸烟。此前，我们和其他人已经证明，cg05575921 的甲基化是成人吸烟状况的准确预测因子。但青少年吸烟后去甲基化反应的剂量和时间依赖性尚不清楚。为此，我们连续三年对 448 名高中生进行了年度面对面访谈和生物采样（第 1 波 (W1) - 第 3 波 (W3)）。在第 1 周（n = 448），62 名受试者报告使用烟草，72 名受试者报告在其一生中至少使用过一次大麻，其中 38 名受试者和 20 名受试者在第 1 周摄入时可替宁和大麻素水平分别呈阳性。在第 3 周（n = 383），67 名受试者报告使用烟草，60 名受试者报告至少使用过一次大麻，其中 75 名受试者和 60 名受试者在第 3 周时可替宁和大麻素水平呈阳性。在整个研究过程中，所有三个时间点可替宁水平均检测不到的受试者的 cg05575921 甲基化水平稳定（第 1 周为 88.7%，第 3 周为 88.8%，n = 149），而在所有 3 个时间点可替宁水平呈阳性的受试者则表现出稳定的 cg05575921 甲基化水平。 cg05575921 甲基化减少（W1 为 81.8%，W3 为 71.3%，n = 12）。在那些在第 3 周有肯定吸烟自我报告的受试者 (n = 17) 中，cg05575921 的去甲基化量与吸烟的时间和强度相关。我们得出结论，cg05575921甲基化是吸烟早期阶段的敏感、剂量依赖性指标，可能有助于识别早期吸烟阶段的吸烟者。