The genetic factors that explain why some people seem to maintain healthy lungs despite a lifetime of smoking have been uncovered by British scientists.
A team funded by the Medical Research Council say their investigations into smokers who survive their habit into old age could hold the key to better treatment for diseases such as chronic obstructive pulmonary disease (COPD).
They say their findings, which have also identified the genetic differences which affect whether a person is more likely to get addicted to cigarettes, could also lead to better interventions to help people quit.
The team, led by Professors Ian Hall at the University of Nottingham and Martin Tobin at the University of Leicester, found certain DNA profiles had a lower risk of COPD – a collection of lung disorders including bronchitis and emphysema – than others, despite external factors such as smoking. These genes appeared to affect the way lungs grow and respond to injury.
On the other hand, there were also certain DNA profiles that had a higher risk of COPD, explaining why some people develop the disease despite never having touched a cigarette in their lives.
However, the findings are not a green light for a lucky few to strike up a 40-a-day habit. Tobin said: “Smoking is the biggest lifestyle risk factor for COPD. Many, but not all, smokers develop the disease. Genetics play a big part, as they do in smoking behaviour.
“Our research helps to tell us why, paving the way for improved prevention and treatment. Stopping smoking is the best way to prevent smoking-related diseases such as COPD, cancers and heart disease.”
Hall and Tobin’s team were also able to identify five sections of DNA shown for the first time to relate to being a heavy smoker. These seemed to affect the brain’s function in response to nicotine, although their precise role still needs to be confirmed. Further investigation could lead to a better understanding of smokers’ addictions, and how to help them beat them.
Hall said: “The drugs we use to prevent or treat diseases target the proteins in our bodies, and our genes influence the production of proteins. Understanding how the genes are involved in disease or in addiction to tobacco, can help us design and develop better and more targeted treatments that are likely to be more effective and have fewer side effects.”
The research used the first analyses of genetic data from participants in the UK Biobank, which has the medical profiles of nearly 500,000 people recruited between 2006 and 2010 when they were aged 40 to 69.
The team selected 50,000 of these participants based on their lung health and whether or not they were heavy smokers or had never smoked.
They compared these factors with 28 million genetic variants in each participant, finding parts of the human genome never before associated with a person’s lung health, as well as the five sections of DNA shown for the first time to relate to being a heavy smoker.
The findings were presented at this year’s European Respiratory Society meeting in Amsterdam and are published in the Lancet Respiratory Medicine.
The Lancet study says: “By sampling from the extremes of the lung function distribution in UK Biobank, we identified novel genetic causes of lung function and smoking behaviour.
“These results provide new insight into the specific mechanisms underlying airflow obstruction, COPD, and tobacco addiction, and show substantial shared genetic architecture underlying airflow obstruction across individuals, irrespective of smoking behaviour and other airway disease.”
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