DNA甲基化生物標記對於吸菸、糖尿病、肺功能之中介效應

Abstract

過去研究已發現吸菸會導致特定 DNA CpG 位點甲基化，進而增加對糖尿病的易感性和引發肺功能下降。本研究旨在探討由 DNA 甲基化生物標記造成的表觀遺傳年齡加速（EAA），是否在亞洲人種中與吸菸、糖尿病、肺功能之間存在中介效應。 本研究對於來自「臺灣人體生物資料庫」的 2,474 名參與者計算了五種不同的 EAA，包括 HannumEAA、IEAA、PhenoEAA、GrimEAA 和 DunedinPACE。結果顯示，GrimEAA、基於 DNA 甲基化的吸菸包年、DNA 甲基化中的第一型胞漿素原活化抑制劑 （PAI-1）、DunedinPACE 和 PhenoEAA 等標記會在吸菸與空腹血糖值和糖化血色素等糖尿病指標間有中介效應。另外，DNA 甲基化中的 PAI-1 也會中介吸菸與用力呼氣肺活量的關係，且戒菸長期來說會間接地透過 GrimEAA 正向影響用力呼氣肺活量。 研究結論表示，由 DNA 甲基化生物標記造成的表觀遺傳年齡加速，在吸菸與健康之間扮演著重要角色。總而言之，吸菸會直接或間接地透過與衰老相關的 DNA CpG 位點甲基化，損害人類健康，而 DNA 甲基化生物標記在此關係中存在中介效應。

Smoking has been found to cause changes in DNA methylation (DNAm) at specific cytosine-phosphate-guanine (CpG) sites, which can result in increased susceptibility to diabetes and decreased lung function. This study investigated the character of epigenetic age acceleration (EAA), caused by DNAm, in connecting the association between smoking and health outcomes related to diabetes and lung function within an Asian population. Five distinct measurements of EAA were assessed in the study, including HannumEAA, IEAA, PhenoEAA, GrimEAA, and DunedinPACE, in 2,474 participants from the Taiwan Biobank. The results indicated that the associations between smoking and health outcomes related to diabetes, such as fasting glucose and hemoglobin A1c were mediated by several DNAm markers, namely GrimEAA, DNAm-based pack-years, DNAm plasminogen activator inhibitor 1 (PAI-1) levels, DunedinPACE, and PhenoEAA. Additionally, DNAm PAI-1 levels acted as a mediator in the relationship between smoking and forced vital capacity (FVC), a lung-related outcome. Furthermore, long-term smoking cessation had a beneficial impact on FVC among former smokers through the mediator GrimEAA. The study’s findings highlight the effect of DNAm on EAA, establishing a crucial connection between smoking and health. It conclusively demonstrates that smoking directly impairs human health and indirectly affects it by inducing changes in DNAm CpG sites associated with aging. These changes in DNAm markers can mediate the complex relationship between smoking and health outcomes.