CitationYao, Yao; Liu, Linxin; Guo, Guang; Zeng, Yi; & Ji, John S. (2021). Interaction of Sirtuin 1 (SIRT1) Candidate Longevity Gene and Particulate Matter (PM2.5) on All-Cause Mortality: A Longitudinal Cohort Study in China. Environmental Health, 20(1), 25. PMCID: PMC7958462
AbstractBACKGROUND: 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.
METHODS: 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(2.5) 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(2.5) exposure on all-cause mortality, adjusting for a set of confounders.
RESULTS: There were 2843 deaths over 42,852 person-years. The mortality hazard ratio (HR) and 95% confidence interval (CI) for each 10 μg/m(3) increase in PM(2·5) 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(3) increase in PM(2.5) 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.
CONCLUSION: 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.
Reference TypeJournal Article
Journal TitleEnvironmental Health
Ji, John S.