長年喫煙していたにもかかわらずわずか１日で禁煙に成功し二度と喫煙しない人がいる一方で、禁煙に苦労する人がいるのはなぜか――その答えが神経伝達物質であるドパミンの機能に変化をもたらす２つの遺伝子にあることが、医学誌「Health Psychology」2003年10月号掲載の米ペンシルバニア大学による研究で明らかになった。

　ドーパミンは脳内で神経細胞間のメッセンジャーとして働く神経伝達物質である。研究では臨床試験に組み入れた418人に対して抗うつ薬ブプロピオンまたはプラセボのいずれかを10週間にわたって投与し、行動カウンセリングを行った。遺伝子分析のために全例で血液採取析を行い、禁煙状態を10週目の終わりと６か月後に評価して同薬の禁煙効果を調べた。

　その結果、ドーパミントランスポーター（輸送）遺伝子（ＳＬＣ６Ａ３）およびドパミンレセプター（受容体）遺伝子（ＤＲＤ２）の特定の変異体をもつ人は、そうでない人に比べ禁煙および再喫煙の回避に成功する率が高いことが判明した。将来的には、禁煙治療に対する反応を左右する患者個人の遺伝子構造に基づいてザイバン（プブロピオン）やパッチ（ニコチン補充療法）などの療法を適格に選択できる可能性が示唆されている。

　しかし、米オクスナー禁煙センター長のRobert Baker氏は「この治療法が確立するまで待っていたのでは生きながらえることができない」とし、「これらの遺伝子がない人には少し大変かもしれないが、それでも何千という成功例があり、必ず禁煙はできる」と断言する。ちなみに現在の米国では男性の約25％、女性の21％が喫煙者であるが、米国対がん協会（ＡＣＳ）によるとすでに4400万人を超える人が禁煙に成功しているという。

[2003年10月10日/HealthDayNews]

RIDAY, Oct. 10 (HealthDayNews) -- Did you ever wonder why some people stop smoking cold turkey and never look back, while others struggle to quit again and again?

Researchers from the Tobacco Use Research Center at the University of Pennsylvania may have found at least part of the answer -- genetics.

Two genes in particular seem to help smokers quit successfully, and this same combination of genes also makes them less likely to start smoking again, report the researchers in the October issue of Health Psychology.

"This study provides the first evidence that genes that alter dopamine function may influence smoking cessation and relapse during treatment," study author Caryn Lerman, associate director for Cancer Control and Population Science at the University of Pennsylvania, says in a press release.

Dopamine is a neurotransmitter that acts as a messenger between nerve cells in the brain.

Lerman and her colleagues studied 418 people who were enrolled in a clinical trial to test the effectiveness of the antidepressant bupropion for smoking cessation. The study participants either received a placebo or bupropion for 10 weeks and behavioral counseling.

Blood samples were taken from all of the participants for genetic analysis. Smoking status was assessed at the end of the 10 weeks and then again after six months.

People who had particular variants of a dopamine transporter gene (SLC6A3) and a dopamine receptor gene (DRD2) were more successful at staying off cigarettes and avoiding relapse than people who didn't have those variants.

"One of the great mysteries in smoking cessation is why some people find it so easy and why it's so hard for others," says Robert Baker, director of the Ochsner Center for the Elimination of Smoking in New Orleans. "I hear about people who have smoked for 40 years and then just put them down one day. Others haven't smoked as long and seem to have a much harder time. I think genetic factors do play a role."

Dr. Marc K. Siegel, an internist at New York University Medical Center, agrees. "It's not surprising to hear that someone's genetic makeup influences their response to quitting smoking. Some patients respond to Zyban [a form of bupropion], some to the patch [nicotine replacement therapy]." Often, people who want to quit are encouraged by doctors to use Zyban and a patch.

What's exciting about this research, Siegel says, is the possibility that one day doctors could specifically target smoking cessation treatment to each patient based on their genetic makeup. But such a therapy is likely a long time away. "If you're waiting for a cure before you quit smoking," advises Baker, "you may not live that long."

Despite some compelling reasons to quit -- including an increased risk of many cancers, heart disease and a one in five chance of developing emphysema or chronic bronchitis, according to the American Cancer Society -- many people still smoke.

About 25 percent of all men and 21 percent of women in the United States are currently smokers, according to the U.S. Centers for Disease Control and Prevention.

The good news is that plenty of people -- with and without these genes -- have quit smoking. The American Cancer Society says that more than 44 million Americans have stopped smoking.

"You may have a more difficult time if you don't have these genes," says Baker, "but you can still get off cigarettes. I'm sure there are thousands upon thousands who have done just that."

More information

For more information on quitting smoking, visit the American Lung Association or the American Cancer Society.

SOURCES: Robert Baker, Ph.D., director, Ochsner Center for the Elimination of Smoking, and director, behavioral medicine unit, Ochsner Clinic Foundation Hospital, New Orleans; Marc K. Siegel, internist, New York University Medical Center, and clinical associate professor, New York University School of Medicine, New York City; October 2003 Health Psychology