Researchers Find Genetic Vulnerability to Menthol Cigarette Use

A genetic variant found only in people of African descent significantly increases a smoker’s preference for cigarettes containing menthol, a flavor additive. The variant of the MRGPRX4 gene is 5 to 8 times more frequent among smokers who use menthol cigarettes than other smokers, according to an international group of researchers supported by the Food and Drug Administration and NIH. The multiethnic study is the first to look across all genes to identify genetic vulnerability to menthol cigarettes. The paper was published online in PLoS Genetics on Feb. 15.

Menthol provides a minty taste and a cooling or soothing sensation and plays a particularly troubling role in U.S. cigarette smoking patterns. 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 percent of African-American smokers use menthol cigarettes, compared to fewer than 30 percent 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, clues as to how menthol may reduce the irritation and harshness of smoking cigarettes were also uncovered by the researchers.

“This study sheds light on the molecular mechanisms of how menthol interacts with the body,” said Dr. Andrew Griffith, scientific director and acting deputy director of 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.”

The researchers report that 5 to 8 percent of the African-American study participants had the gene variant. None of the participants of European, Asian or Native American descent had the variant.

“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 NIDCD’s Dr. Dennis 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.”