Yao Yao1, Linxin Liu2, Guang Guo3, Yi Zeng1,4, John S Ji5,6. 1. Center for Healthy Aging and Development Studies, National School of Development, Peking University, Beijing, China. 2. Environmental Research Center, Duke Kunshan University, 22 Address: No. 8 Duke Avenue, Kunshan, 215316, Jiangsu, China. 3. Department of Sociology, Carolina Population Center, and Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 4. Center for the Study of Aging and Human Development, Duke Medical School, Durham, NC, USA. 5. Environmental Research Center, Duke Kunshan University, 22 Address: No. 8 Duke Avenue, Kunshan, 215316, Jiangsu, China. john.ji@dukekunshan.edu.cn. 6. Nicholas School of the Environment, Duke University, Durham, NC, USA. john.ji@dukekunshan.edu.cn.
Abstract
BACKGROUND: 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 PM2.5 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 PM2.5 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/m3 increase in PM2·5 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/m3 increase in PM2.5 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.
BACKGROUND: 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 PM2.5 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 PM2.5 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/m3 increase in PM2·5 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/m3 increase in PM2.5 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.
Entities:
Keywords:
Air pollution; CLHLS; Longevity gene; Sex difference
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