Credit: Copyright American Heart Association
Smoking leaves its "footprint" on the
human genome in the form of DNA methylation, a process by which cells
control gene activity, according to new research in Circulation: Cardiovascular Genetics, an American Heart Association journal.
The new findings suggest that DNA methylation could be an important
sign that reveals an individual's smoking history, and could provide
researchers with potential targets for new therapies.
"These results are important because methylation, as one of the
mechanisms of the regulation of gene expression, affects what genes are
turned on, which has implications for the development of smoking-related
diseases," said Stephanie J. London, M.D., Dr.P.H., last author and
deputy chief of the Epidemiology Branch at the National Institute of
Environmental Health Sciences, National Institutes of Health, Research
Triangle Park, North Carolina. "Equally important is our finding that
even after someone stops smoking, we still see the effects of smoking on
their DNA."
Smoking remains the leading preventable cause of death worldwide,
despite a decline in smoking in many countries as a result of smoking
cessation campaigns and legislative action. Even decades after stopping,
former smokers are at long-term risk of developing diseases including
some cancers, chronic obstructive pulmonary disease, and stroke. While
the molecular mechanisms responsible for these long-term effects remain
poorly understood, previous studies linking DNA methylation sites to
genes involved with coronary heart disease and pulmonary disease suggest
it may play an important role.
Researchers conducted a meta-analysis of DNA methylation sites across
the human genome using blood samples taken from nearly 16,000
participants from 16 groups of the Cohorts for Heart and Aging Research
in Genetic Epidemiology (CHARGE) Consortium, including a group of the
Framingham Heart Study that has been followed by researchers since 1971.
The researchers compared DNA methylation sites in current and former smokers to those who never smoked.
They found:
- Smoking-associated DNA methylation sites were associated with more than 7,000 genes, or one-third of known human genes.
- For people who stopped smoking, the majority of DNA methylation sites returned to levels seen in never smokers within five years of quitting smoking.
- However, some DNA methylation sites persisted even after 30 years of quitting.
- The most statistically significant methylation sites were linked to genes enriched for association with numerous diseases caused by cigarette smoking, such as cardiovascular diseases and certain cancers.
The
researchers suggest that some of these long-lasting methylation sites
may be marking genes potentially important for former smokers who are
still at increased risk of developing certain diseases. The discovery of
smoking-related DNA methylation sites raises the possibility of
developing biomarkers to evaluate a patient's smoking history, as well
as potentially developing new treatments targeted toward these
methylation sites.
The main analysis was not designed to examine effects over long
periods of time. The researchers note, that this is the largest
examination of the effects of smoking on DNA methylation.
"Our study has found compelling evidence that smoking has a
long-lasting impact on our molecular machinery, an impact that can last
more than 30 years," said Roby Joehanes Ph.D. of Hebrew SeniorLife,
first author and an instructor at Harvard Medical School in Boston,
Massachusetts. "The encouraging news is that once you stop smoking, the
majority of DNA methylation signals return to never smoker levels after
five years, which means your body is trying to heal itself of the
harmful impacts of tobacco smoking."
https://www.sciencedaily.com/releases/2016/09/160921215106.htm
No comments:
Post a Comment