Smoking Alters DNA-based Mechanism That Influences Gene Activity in MS, Study Confirms

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Smoking and MS mechanism

Smoking changes a DNA-based mechanism that influences multiple sclerosis patients’ gene activity, a Swedish study confirms.

Another finding was that MS appears to aggravate the harmful effects of smoking.

The study dealt with DNA methylation, the process by which the body adds methyl groups to a DNA molecule. Methylation can change a DNA segment’s activity without changing the sequence. Smoking changes the way methylation works, which means it can also change gene activity.

The study, “Smoking induces DNA methylation changes in Multiple Sclerosis patients with exposure-response relationship,” was published in the journal Scientific Reports.

MS is a chronic, progressive neurodegenerative disorder. It occurs when the body’s own immune system attacks the central nervous system, which consists of the brain, spinal cord and optical nerves.

Scientists have learned that the disease is based on complex interactions between environmental and genetic factors.

Recently they discovered that epigenetic changes may play a key role in MS development. Epigenetics involves mechanisms that influence genes’ activity without altering the underlying DNA sequence. One of these mechanisms is DNA methylation.

Tagging genes with chemical flags such as methyls allows or prevents certain gene activity. These flags are not constant, able to be attached and removed in response to environmental factors.

Cigarette smoking, which increases the risk of a person developing MS and the disease progressing, reduces DNA methylation levels. The number of cigarettes a person smokes not only affects methylation levels but also increases the risk of a person developing MS. But smoking’s effects on MS are reversible once the person quits.

Swedish researchers decided to build on these findings by investigating how smoking affects DNA methylation in the blood of MS patients.

Their study covered 50 women with MS who also had genetic risk factors for the disease, 132 other MS patients, and 135 healthy people.

The team divided the participants into three categories: smokers, former smokers, and people who had never smoked.

Their key finding was that smoking significantly affected MS patients’ DNA methylation pattern by reducing methylation levels. The more a person smoked, the worse the impact, the team discovered. When a smoker quit, the impact diminished more and more over time, they added

“We verified that smoking has a genome-wide significant effect on blood DNA methylation in MS patients, and that the effect is especially evident in current smokers and patients” who stopped smoking less than five years before the study, the researchers wrote.

These changes were greater in women with genetic risk factors associated with MS.

The team also found that MS smokers’ AHRR gene had significantly lower levels of methylation. AHRR, which responds to environmental cues, helps control immune responses, particularly nerve cell inflammation.

“In this context, epigenetic processes (DNA methylation) are likely to contribute to the response to environmental exposures (smoking), by mediating or altering the impact of the external trigger on the gene expression networks and cellular function during neuroinflammation,” the researchers wrote.

Although smoking a lot significantly reduced DNA methylation in both MS patients and healthy subjects, the effect was stronger in MS patients. This suggested that MS aggravates the effects of smoking a lot, including reducing methylation.

“Both from a public health and pathogenetic [disease-treating] perspective, the impact of smoking has a fundamental importance in the understanding and the management of MS,” the team wrote. “Therefore the findings presented here provide clues for further study of the connection between the environment and the reversible epigenetic changes observed in MS patients” who smoke, they wrote.

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