一种用于预测全因死亡率的吸烟 droplet 数字 PCR 检测方法。
A Droplet Digital PCR Assay for Smoking Predicts All-Cause Mortality.
作者信息
Andersen Allan M, Ryan Philip T, Gibbons Fredrick X, Simons Ronald L, Long Jeffrey D, Philibert Robert A
机构信息
1 Department of Psychiatry, University of Iowa, Iowa City, IA, USA 52242.
2 Department of Psychological Sciences, University of Connecticut, Storrs, CT 06269.
出版信息
J Insur Med. 2018;47(4):220-229. doi: 10.17849/insm-47-4-1-10.1. Epub 2019 Jan 31.
OBJECTIVES
-Determine whether an epigenetic assay for smoking predicts all-cause mortality in adults participating in a longitudinal study of Iowa adoptees.
BACKGROUND
-Improved biomarkers for smoking are needed given its large public health impact and significant limitations of both self-report and current biomarkers, such as cotinine in detecting smoking. In the past 5 years, multiple epigenome-wide association studies of smoking have identified loci suitable for translation as epigenetic biomarkers for smoking, in particular the CpG cg05575921. Digital polymerase chain reaction methods hold promise for the development of this and other epigenetic biomarkers.
METHODS
-Participants in the Iowa Adoption Studies were interviewed regarding their smoking habits. DNA was prepared from whole blood and bisulfite-converted for methylation analysis and digital droplet polymerase chain reaction assay of methylation at cg05575921 was performed. National Death Index records were requested for 584 study participants, resulting in 24 complete matches, 210 partial matches and 350 non-matching records. Complete matches were coded as deceased while the remainder were coded as alive (ie, censored). In total, methylation data and vital status information were available for a total of N = 193 subjects, including 15 deceased and 178 non-deceased. Cox regression was used to examine the ability of cg05575921 methylation as a continuous value to predict the timing of mortality with and without the inclusion of age, sex, race, BMI, marital status, educational status, socioeconomic status, cardiovascular risk factors, and a history of cancer as covariates.
RESULTS
-Methylation at cg05575921 predicted the hazard of mortality as the sole predictor and after accounting for major demographic and clinical risk factors. The fitted model showed the hazard ratio increased by 3.5% for every 1% decrease in methylation.
CONCLUSIONS
-Decreased methylation at cg05575921, an emerging epigenetic biomarker for smoking, was associated with early mortality in a longitudinal study of adults after accounting for the impact of major demographic and clinical risk factors for all-cause mortality. This approach may be useful in clinical research or actuarial assessments.
目标
确定一种用于吸烟的表观遗传学检测方法能否预测参与爱荷华州领养者纵向研究的成年人的全因死亡率。
背景
鉴于吸烟对公共卫生的巨大影响以及自我报告和当前生物标志物（如可替宁在检测吸烟方面）的显著局限性，需要改进吸烟的生物标志物。在过去5年中，多项吸烟的全表观基因组关联研究确定了适合转化为吸烟表观遗传生物标志物的位点，特别是CpG cg05575921。数字聚合酶链反应方法有望用于开发这种及其他表观遗传生物标志物。
方法
对爱荷华州领养研究的参与者进行吸烟习惯访谈。从全血中提取DNA并进行亚硫酸氢盐转化用于甲基化分析，并对cg05575921处的甲基化进行数字液滴聚合酶链反应检测。向国家死亡指数记录机构申请了584名研究参与者的记录，得到24个完全匹配、210个部分匹配和350个不匹配记录。完全匹配的记录编码为已故，其余编码为存活（即删失）。总共，有N = 193名受试者的甲基化数据和生命状态信息可用，包括15名已故和178名未已故者。使用Cox回归来检验cg05575921甲基化作为连续值在纳入和不纳入年龄、性别、种族、体重指数、婚姻状况、教育状况、社会经济状况、心血管危险因素和癌症病史作为协变量的情况下预测死亡时间的能力。
结果
cg05575921处的甲基化作为唯一预测因子以及在考虑主要人口统计学和临床危险因素后预测了死亡风险。拟合模型显示，甲基化每降低1%，风险比增加3.5%。
结论
在一项成年人纵向研究中，在考虑了全因死亡率的主要人口统计学和临床危险因素的影响后，新兴的吸烟表观遗传生物标志物cg05575921处甲基化降低与早期死亡相关。这种方法可能在临床研究或精算评估中有用。
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