Basic Neurosciences, Genetics and Immunology - Original Article

Journal of Neural Transmission

, Volume 119, Issue 12, pp 1491-1498

First online:

Association of functional COMT Val108/Met polymorphism with smoking cessation in a nicotine replacement therapy

  • Hongqiang SunAffiliated withBeijing Hui-Long-Guan HospitalThe National Institute on Drug Dependence, Peking University
  • , Song GuoAffiliated withNational Drug Abuse Treatment Center, Beijing Anding Hospital Affiliated Capital University of Medical SciencesAddiction Medicine Department, Institute of Mental Health Email author 
  • , Dafang ChenAffiliated withDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University
  • , Fude YangAffiliated withBeijing Hui-Long-Guan Hospital
  • , Yizhuang ZouAffiliated withBeijing Hui-Long-Guan Hospital
  • , Xiaolan DiAffiliated withBeijing Hui-Long-Guan Hospital
  • , Yanjun CaoAffiliated withBeijing Hui-Long-Guan Hospital
  • , Thomas KostenAffiliated withDepartment of Psychiatry and Behavioral Sciences, Baylor College of Medicine
  • , Lin LuAffiliated withThe National Institute on Drug Dependence, Peking University
    • , Xiang Yang ZhangAffiliated withBeijing Hui-Long-Guan HospitalDepartment of Psychiatry and Behavioral Sciences, Baylor College of MedicineVA Medical Center Email author 

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Nicotine replacement treatment (NRT) can be efficacious for smoking cessation, but used by only a minority of smokers in China. Pharmacogenetic matching may improve treatment outcomes for NRT in subgroups of smokers. We evaluated the efficacy and safety of sublingual nicotine tablets (SNT) for smoking cessation and the association of catechol-O-methyltransferase (COMT) genotype with efficacy in this smoking cessation trial among Chinese smokers. We conducted a double-blind, placebo-controlled, 8-week trial of SNT with a follow-up at week 12 among 250 Chinese smokers. Efficacy and safety were evaluated at day 4 and weeks 2, 4, 6, 8, and 12. Abstinence was biochemically verified by exhaled carbon monoxide (CO) and urine cotinine. The COMT Val108Met genotype was determined as a restriction fragment length polymorphism. Our results showed that the success rates for complete abstinence were greater for active versus placebo treatments at 8 weeks (48 vs. 17 %) and 12 weeks (52 vs. 19 %) (both p < 0.0001). Craving was significantly reduced from week 2 on active treatment compared to placebo. Adverse events were mild and tolerable. We found a genotype by treatment interaction at 12 weeks with greater abstinence rates in the COMT Val/Val (50 vs. 15 %) than the Met/Val + Met/Met genotypes (46 vs. 25 %). We found that SNT significantly increased smoking abstinence, reduced craving and was well tolerated, and the COMT Val/Val genotype was associated with a greater improvement in smoking cessation.


Pharmacogenetics COMT Nicotine dependence Smoking Dopamine