Center for Healthy Aging and Development Studies, National School of Development, Peking University, Beijing, China.
Environmental Research Center, Duke Kunshan University, 22 Address: No. 8 Duke Avenue, Kunshan, 215316, Jiangsu, China.
Environ Health. 2021 Mar 14;20(1):25. doi: 10.1186/s12940-021-00718-x.
The SIRT1 gene was associated with the lifespan in several organisms through inflammatory and oxidative stress pathways. Long-term air particulate matter (PM) is detrimental to health through the same pathways.
We used the Chinese Longitudinal Healthy Longevity Survey (CLHLS) to investigate whether there is a gene-environment (G × E) interaction of SIRT1 and air pollution on mortality in an older cohort in China. Among 7083 participants with a mean age of 81.1 years, we genotyped nine SIRT1 alleles for each participant and assessed PM concentration using 3-year average concentrations around each participant's residence. We used Cox-proportional hazards models to estimate the independent and joint effects of SIRT1 polymorphisms and PM exposure on all-cause mortality, adjusting for a set of confounders.
There were 2843 deaths over 42,852 person-years. The mortality hazard ratio (HR) and 95% confidence interval (CI) for each 10 μg/m increase in PM was 1.08 (1.05-1.11); for SIRT1_391 was 0.77 (0.61, 0.98) in the recessive model after adjustment. In stratified analyses, participants carrying two SIRT1_391 minor alleles had a significantly higher HR for each 10 μg/m increase in PM than those carrying zero minor alleles (1.323 (95% CI: 1.088, 1.610) vs. 1.062 (1.028, 1.096) p for interaction = 0.03). Moreover, the interaction of SIRT1 and air pollution on mortality is significant among women but not among men. We did not see significant relationships for SIRT1_366, SIRT1_773, and SIRT1_720.
We found a gene-environment interaction of SIRT1 and air pollution on mortality, future experimental studies are warranted to depict the mechanism observed in this study.
SIRT1 基因通过炎症和氧化应激途径与几种生物的寿命有关。长期的空气颗粒物（PM）通过相同的途径对健康有害。
我们使用中国长寿纵向研究（CLHLS）来调查 SIRT1 基因和空气污染对中国老年队列死亡率是否存在基因-环境（G×E）相互作用。在 7083 名平均年龄为 81.1 岁的参与者中，我们对每个参与者的 9 个 SIRT1 等位基因进行了基因分型，并使用每个参与者居住地周围的 3 年平均浓度评估了 PM 浓度。我们使用 Cox 比例风险模型来估计 SIRT1 多态性和 PM 暴露对全因死亡率的独立和联合影响，同时调整了一系列混杂因素。
在 42852 人年中，发生了 2843 例死亡。PM 每增加 10μg/m 的死亡率危险比（HR）和 95%置信区间（CI）为 1.08（1.05-1.11）；调整后，在隐性模型中，SIRT1_391 为 0.77（0.61, 0.98）。在分层分析中，与携带零个次要等位基因的参与者相比，携带两个 SIRT1_391 次要等位基因的参与者 PM 每增加 10μg/m 的 HR 显著更高（1.323（95%CI：1.088, 1.610）与 1.062（1.028, 1.096），p 交互=0.03）。此外，SIRT1 与空气污染对死亡率的相互作用在女性中显著，但在男性中不显著。我们没有发现 SIRT1_366、SIRT1_773 和 SIRT1_720 之间存在显著关系。
我们发现 SIRT1 基因和空气污染对死亡率存在基因-环境相互作用，需要进一步的实验研究来描述本研究中观察到的机制。
