Scientists find genetic vulnerability to menthol cigarette use

The study is the first to look across all genes to identify genetic vulnerability to menthol cigarettes.

Scientists have now found a genetic variant in people of African descent that significantly increases a smoker’s preference for cigarettes containing menthol, a flavour additive.

Although not originally the focus of the study, researchers also uncovered clues as to how menthol may reduce the irritation and harshness of smoking cigarettes. (Unsplash)

According to scientists the variant of the MRGPRX4 gene is five to eight times more frequent among smokers who use menthol cigarettes than other smokers, according to an international group of researchers supported by the U.S. Food and Drug Administration and the National Institutes of Health. The study is the first to look across all genes to identify genetic vulnerability to menthol cigarettes. The paper was published online in the journal PLOS Genetics.

According to the FDA, nearly 20 million people in the United States smoke menthol cigarettes, which are particularly popular among African-American smokers and teen smokers. In the U.S., 86% of African-American smokers use menthol cigarettes, compared to less than 30% of smokers of European descent. In addition, menthol cigarettes may be harder to quit than other cigarettes.

Although not originally the focus of the study, researchers also uncovered clues as to how menthol may reduce the irritation and harshness of smoking cigarettes.

Study author Andrew Griffith said, “This study sheds light on the molecular mechanisms of how menthol interacts with the body,” adding, “These results can help inform public health strategies to lower the rates of harmful cigarette smoking among groups particularly vulnerable to using menthol cigarettes.”

Identifying the genetic variant pointed the researchers in an unexpected direction, leading them to provide the first characterisation of this naturally-occurring MRGPRX4 variant in humans. The gene codes for a sensor, or receptor, that is believed to be involved in detecting and responding to irritants from the environment in the lungs and airways.

“We expected to find genes that relate to taste receptors, since menthol is a flavour additive,” said Drayna. “Instead, we discovered a different kind of signalling molecule that appears to be involved in menthol preference.”

Collaborators at the University of North Carolina (UNC), Chapel Hill, then worked with the research team to look more closely at the effect of the African-specific variant on the function of the MRGPRX4 receptor. They found that the variant alters a specific type of cell signaling, and that menthol alters this further. Additional studies confirmed that this sensor is found in the airways, suggesting that menthol is likely to affect how we sense irritation in the airways.

Drayna added that while the gene variant can’t explain all of the increased use of menthol cigarettes by African-Americans, the findings indicate that this variant is a potentially important factor that underlies the preference for menthol cigarettes in the population.

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