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Interaction of Sirtuin 1 (SIRT1) candidate longevity gene and particulate matter (PM2.5) on all-cause mortality: a longitudinal cohort study in China
John S. Ji
Duke Kunshan University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5002-118X
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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 7,083 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 2,843 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.
Keywords
Longevity gene, Air pollution, Sex difference, CLHLS
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CURRENT STATUS: Under Review
Version 2
Posted 26 Jan, 2021
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Reviewer #2 agreed
On 26 Jan, 2021
Review #1 received
Received 25 Jan, 2021
Editor assigned
On 17 Jan, 2021
Reviewers invited
Invitations sent on 17 Jan, 2021
Reviewer #1 agreed
On 17 Jan, 2021
Submission checks complete
On 17 Jan, 2021
Editor invited
On 17 Jan, 2021
No comments provided
Editorial decision: Major revision
On 16 Dec, 2020
Review #2 received
Received 14 Dec, 2020
Reviewer #2 agreed
On 13 Dec, 2020
Review #1 received
Received 28 Sep, 2020
Reviewers invited
Invitations sent on 16 Sep, 2020
Reviewer #1 agreed
On 16 Sep, 2020
Editor assigned
On 15 Sep, 2020
First submitted
On 14 Sep, 2020
Submission checks complete
On 14 Sep, 2020
Editor invited
On 14 Sep, 2020
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Subject Areas
Environmental Engineering
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This preprint is under consideration at Environmental Health. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Interaction of Sirtuin 1 (SIRT1) candidate longevity gene and particulate matter (PM2.5) on all-cause mortality: a longitudinal cohort study in China
John S. Ji
Duke Kunshan University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5002-118X
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 2
Posted 26 Jan, 2021
No community comments so far
Reviewer #2 agreed
On 26 Jan, 2021
Review #1 received
Received 25 Jan, 2021
Editor assigned
On 17 Jan, 2021
Reviewers invited
Invitations sent on 17 Jan, 2021
Reviewer #1 agreed
On 17 Jan, 2021
Submission checks complete
On 17 Jan, 2021
Editor invited
On 17 Jan, 2021
No comments provided
Editorial decision: Major revision
On 16 Dec, 2020
Review #2 received
Received 14 Dec, 2020
Reviewer #2 agreed
On 13 Dec, 2020
Review #1 received
Received 28 Sep, 2020
Reviewers invited
Invitations sent on 16 Sep, 2020
Reviewer #1 agreed
On 16 Sep, 2020
Editor assigned
On 15 Sep, 2020
First submitted
On 14 Sep, 2020
Submission checks complete
On 14 Sep, 2020
Editor invited
On 14 Sep, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Environmental Engineering
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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 7,083 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 2,843 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.
Figure 1
Figure 2