Gene Behind Preference for Menthol Cigarettes Identified

Scientists have identified a gene that increases a smoker's preference for cigarettes containing menthol, a flavour additive that provides a minty taste and a cooling or soothing sensation.

According to researchers, including those from University of Texas Southwestern in the US, the variant of the MRGPRX4 gene is five to eight times more frequent among smokers who use menthol cigarettes than other smokers.

The multiethnic study, published in the journal PLOS Genetics, is the first to look across all genes to identify genetic vulnerability to menthol cigarettes.

Menthol cigarettes may be harder to quit than other cigarettes, researchers said.

The team also uncovered clues as to how menthol may reduce the irritation and harshness of smoking cigarettes.

This study sheds light on the molecular mechanisms of how menthol interacts with the body. These results can help inform public health strategies to lower the rates of harmful cigarette smoking among groups particularly vulnerable to using menthol cigarettes.

Andrew Griffith, scientific director of US National Institute on Deafness and Other Communications Disorders (NIDCD)

The team conducted detailed genetic analyses on 1,300 adults. They found that five to eight per cent of the African-American study participants had the gene variant.

None of the participants of European, Asian, or Native American descent had the variant.

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. Instead, we discovered a different kind of signaling molecule that appears to be involved in menthol preference.

Dennis Drayna, chief of the Section on Genetics of Communication Disorders at the NIDCD

Researchers looked 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.

"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," said Drayna.

"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," he said.