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Vaping linked to dysregulation of genes and disruption of molecular pathways involved in immunity and inflammatory response

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Adult smokers have been touting e-cigarettes as a safe alternative to traditional cigarettes since they first entered the market. When studies began to demonstrate differently, many people wondered if smoking was still to blame for the negative consequences, given that the majority of vapers are either “dual users” who also smoke cigarettes or have a smoking history.

Now, a team of researchers from USC’s Keck School of Medicine has shown that consuming e-cigarettes is associated with harmful biological changes that can lead to disease, regardless of the effects of prior smoking.

The study, which was published in Scientific Reports, found that vapers had a similar pattern of gene regulatory modifications as smokers, however, the changes are more extensive in smokers.

“Our study, for the first time, investigates the biological effects of vaping in adult e-cigarette users, while simultaneously accounting for their past smoking exposure,” said Ahmad Besaratinia, PhD, corresponding author and professor of research population and public health sciences at the Keck School of Medicine.  

“Our data indicate that vaping, much like smoking, is associated with dysregulation of mitochondrial genes and disruption of molecular pathways involved in immunity and the inflammatory response, which govern health versus disease state,” says Ahmad Besaratinia – corresponding author and professor at the Keck School of Medicine.

The researchers gathered 82 healthy adults and divided them into three groups: current vapers, both with and without a smoking history; those who only smoke cigarettes; and a control group of never-smokers and never-vapers. They performed in-person interviews with each participant to obtain a full history of vaping and smoking. The subjects’ histories were verified using biochemical examinations of their blood, which measured the levels of cotinine, a breakdown product of nicotine.

Researchers then used next-generation sequencing and bioinformatic data processing to undertake a genome-wide search for alterations in gene regulation in each of the participants’ blood cells. When genes’ regular regulation is interrupted, genes become dysregulated, which can interfere with gene function and lead to disease.

They used computational modeling on current vapers to see if the discovered gene dysregulation was linked to the intensity and duration of their present vaping or the intensity and duration of their previous smoking.

“We found that more than 80% of gene dysregulation in vapers correlated with the intensity and duration of current vaping,” says Besaratinia. “Whereas none of the detected gene dysregulation in vapers correlated to their prior smoking intensity or duration.”

Besaratinia and his colleagues previously demonstrated that e-cigarette users have some of the same cancer-related biochemical alterations in oral tissue as cigarette smokers. They also discovered that vapers’ genomes exhibited the same cancer-linked chemical alterations as smokers’.

They discovered that mitochondrial genes are favored targets of gene dysregulation in both smokers and vapers in this investigation. They also discovered that vapers and smokers had considerable immune response gene dysregulation.

The discoveries, according to Besaratinia, are not only novel and noteworthy, but also interconnected, because emerging data suggests that mitochondria play a key role in immunity and inflammation.

“When mitochondria become dysfunctional, they release key molecules,” says Besaratinia. “The released molecules can function as signals for the immune system, triggering an immune response that leads to inflammation, which is not only important for maintaining health but also plays a critical role in the development of various diseases, such as cardiovascular and respiratory diseases, metabolic diseases, and cancer.”

Adults aren’t the only ones who use e-cigarettes. More than 2 million middle and high school children in the United States use e-cigarettes, according to the Centers for Disease Control and Prevention. This, according to Besaratinia, is one of the key reasons why the team’s research is so important for guiding vaping policy.

“Given the popularity of e-cigarettes among young never-smokers, our findings will be of importance to the regulatory agencies,” says the author. “To protect public health, these agencies are in urgent need of scientific evidence to inform the regulation of the manufacture, distribution, and marketing of e-cigarettes.”

The team’s next step will be to identify and examine compounds found in both e-cigarette vapor and cigarette smoke to see which ones may be generating similar negative effects in both vapers and smokers.

Source: 10.1038/s41598-021-01965-1

Image Credit: iStock

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