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

  • Basic Neurosciences, Genetics and Immunology - Original Article
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Abstract

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.

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Acknowledgments

This projects was supported by grants from the National Natural Science Foundation of China (No. 81071080) and Training Program Foundation for Excellent Talents by the Beijing Municipal Government, China (No. 2010D003034000026), the Stanley Medical research Institute (03T-459 and 05T-726), and the Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC), United States National Institute of Health K05-DA0454, P50-DA18827 and U01-MH79639.

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Correspondence to Song Guo or Xiang Yang Zhang.

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Sun, H., Guo, S., Chen, D. et al. Association of functional COMT Val108/Met polymorphism with smoking cessation in a nicotine replacement therapy. J Neural Transm 119, 1491–1498 (2012). https://doi.org/10.1007/s00702-012-0841-8

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  • DOI: https://doi.org/10.1007/s00702-012-0841-8

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