Researchers discover a genetic vulnerability to the use of menthol cigarettes


Press release

Friday, February 15, 2019

An FDA and NIH-funded study revealed an unexpected sensory variant exclusive to African Americans.

A genetic variant found only in people of African descent greatly increases the smoker's preference for cigarettes containing menthol, an aromatic additive. The variant of MRGPRX4 The gene is five to eight times more common in smokers who use menthol cigarettes than in other smokers, according to an international group of researchers supported by the US Food and Drug Administration and the National Institutes of Health. This multiethnic study is the first to examine all genes to identify genetic vulnerability to menthol cigarettes. The document was published online in the journal PLOS Genetics on February 15th.

Menthol provides a minty, refreshing or soothing sensation and plays a particularly troubling role in cigarette smoking habits in the United States. According to the FDA, nearly 20 million people in the United States smoke menthol cigarettes, which are particularly popular among African-American smokers and teenage smokers. In the United States, 86% of African American smokers use menthol cigarettes, compared to less than 30% of smokers of European descent. In addition, menthol cigarettes may be more difficult to stop than other cigarettes.

Although the study did not focus initially on this study, the researchers also revealed clues as to how menthol could reduce the irritation and hardness of the cigarette.

"This study highlights the molecular mechanisms of how menthol interacts with the body," said Andrew Griffith, MD, Ph.D., Scientific Director and Acting Deputy Director of the National Institute of NIH on deafness and other communication disorders (NIDCD). "These findings can help inform public health strategies aimed at reducing rates of harmful smoking among groups particularly vulnerable to the use of menthol cigarettes."

The research team, headed by Dennis Drayna, Ph.D., head of the section on Genetics of Communication Disorders at NIDCD, conducted detailed genetic analyzes on 1,300 adults. In the initial analyzes, researchers at the University of Texas Southwestern Medical Center in Dallas (UT Southwestern) used data from a group of multiethnic smokers from the Dallas Heart Study population and a group of smokers. African Americans from Dallas. Biobank. In collaboration with researchers from the Schroeder Institute® For Tobacco Research, Washington, DC, scientists also confirmed their findings in a group of African-American smokers enrolled in Washington, DC, Tobacco Quitline.TM.

The researchers reported that 5 to 8% of participants in the African-American study had the gene variant. None of the participants of European, Asian or Native American origin had the variant.

The identification of the genetic variant oriented the researchers in an unexpected direction, leading them to provide the first characterization of this natural phenomenon. MRGPRX4 variant in humans. The gene codes for a sensor, or receptor, that would be involved in detecting and responding to environmental irritants in the lungs and airways.

"We expected to find genes related to taste receptors because menthol is an aromatic additive," Drayna said. "Instead, we discovered a different type of signaling molecule that seems to be involved in menthol preference."

Chapel Hill, researchers at the University of North Carolina (UNC), then collaborated with the research team to look more closely at the effect of the Africa-specific variant on MRGPRX4 receptor function. . They discovered that the variant modified a specific type of cellular signaling and that menthol modified it more. Additional studies have confirmed that this sensor is found in the airways, suggesting that menthol is likely to affect the way we perceive respiratory tract irritation.

"Although this variant of the gene can not explain the increase in menthol smoking by African Americans, our results indicate that this variant is a potentially important factor underlying the preference of menthol cigarettes in this population. Although factors such as cultural factors or advertising practices of the industry have hitherto been at the heart of understanding the use of menthol, our results indicate that genetic factors specific to Africa must also be taken into account, "Drayna said.

The FDA has solicited public comment and scientific information on the use of menthol in tobacco products. The agency has announced its intention to propose a ban on menthol-flavored cigarettes and cigars, largely because of the high consumption of menthol cigarettes among young people and young adults. More than half of smokers aged 12 to 17 smoke menthol cigarettes. According to the FDA, this prevalence reaches 7 out of 10 among young African-Americans who smoke.

In addition to UT Southwestern and UNC Chapel Hill, the research collaborators belonged to the National Complementary and Integrative Health Care Center at NIH; the University of Bologna, Italy; the Estonian biocentre, Tartu; University of California, Merced; and the Schroeder Institute® for tobacco research.

This study was funded in part by the NIH intramural research program and the FDA as part of an inter-agency agreement funded through the Prevention of Smoking and Smoking in the Family Act, as well as through the NIH through the NIDCD (HHSN263201300011C and Z1A000046-16), the National Center for Advancing Translational Science (UL1TR001105), the National Institute of Mental Health (U01MH104974), the National Institute of Neurological Disorders and Stroke (F31NS093917) and the NIH Director's Office through the National Institute of Addiction (RC1-DA028710) Illuminating the Genome Druggable Common Fund Initiative (U24DK116195).

About the National Institute of Deafness and Other Communication Disorders (NIDCD): NIDCD supports and conducts research and training in research on the normal and disordered processes of hearing, balance, taste, smell, voice, speech and language and provides public health information, based on scientific findings.

About the National Institutes of Health (NIH):
The NIH, the country's medical research agency, has 27 institutes and centers and is part of the US Department of Health and Human Services. NIH is the lead federal agency that conducts and supports basic, clinical and translational medical research. She studies causes, treatments and cures for common and rare diseases. For more information on NIH and its programs, visit

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