Researchers have found a small change in a gene called MRGPRX4 that is linked to a significant increase in the preference for menthol cigarettes. The genetic variant was identified only in people of African descent and is five to eight time more common in smokers that prefer menthol cigarettes compared to other smokers. This multiethnic study is the first to find a genetic vulnerability to menthol cigarettes and has been reported in PLOS Genetics.
Menthol influences smoking patterns in the US, and the FDA estimates that about 20 million people smoke menthol cigarettes, which have a cooling sensation. About 30 percent of smokers of European descent use menthol, while around 86 percent of smokers of African descent smoke menthols. Menthol cigarettes may be more challenging for users to quit compared to regular cigarettes.
"This study sheds light on the molecular mechanisms of how menthol interacts with the body," said Andrew Griffith, M.D., Ph.D., scientific director and acting deputy director of NIH's National Institute on Deafness and Other Communications Disorders (NIDCD). "These results can help inform public health strategies to lower the rates of harmful cigarette smoking among groups particularly vulnerable to using menthol cigarettes."
For this work, researchers gathered genetic data from 1,300 adult smokers that were of various ethnicities. The variation in the MRGPRX4 gene was found in five to eight percent of African-American participants, and none of the individuals of Native American, Asian or European descent.
The researchers, surprised by their findings, were then led to characterize MRGPRX4, which encodes for a receptor thought to detect environmental irritants in the airways and lungs. "We expected to find genes that relate to taste receptors since menthol is a flavor additive," said study leader Dennis Drayna, Ph.D., chief of the Section on Genetics of Communication Disorders at the NIDCD. "Instead, we discovered a different kind of signaling molecule that appears to be involved in menthol preference."
The variation identified in this work impacts cell signaling through this receptor, and menthol changes it even more. "While this gene variant can't explain all of the increased use of menthol cigarettes by African-Americans, our findings indicate that this variant is a potentially important factor that underlies the preference for menthol cigarettes in this population. While things like cultural factors or industry advertising practices have been a focus for understanding menthol use thus far, our findings indicate that African-specific genetic factors also need to be considered," said Drayna.
The FDA is interested in imposing a ban on menthol flavoring in tobacco products. Learn more from the video.