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.
Similar content being viewed by others
References
Apud JA, Weinberger DR (2007) Treatment of cognitive deficits associated with schizophrenia: potential role of catechol-O-methyltransferase inhibitors. CNS Drugs 21(7):535–557
Berrettini WH, Lerman CE (2005) Pharmacotherapy and pharmacogenetics of nicotine dependence. Am J Psychiatry 162(8):1441–1451
Berrettini WH, Wileyto EP, Epstein L, Restine S, Hawk L, Shields P et al (2007) Catechol-O-methyltransferase (COMT) gene variants predict response to bupropion therapy for tobacco dependence. Biol Psychiatry 61(1):111–118
Beuten J, Payne TJ, Ma JZ, Li MD (2006) Significant association of catechol-O-methyltransferase (COMT) haplotypes with nicotine dependence in male and female smokers of two ethnic populations. Neuropsychopharmacology 31(3):675–684
Chen J, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S et al (2004) Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. Am J Hum Genet 75(5):807–821
Colilla S, Lerman C, Shields PG, Jepson C, Rukstalis M, Berlin J et al (2005) Association of catechol-O-methyltransferase with smoking cessation in two independent studies of women. Pharmacogenet Genomics 15(6):393–398
David SP, Johnstone E, Griffiths SE, Murphy M, Yudkin P, Mant D et al (2002) No association between functional catechol O-methyl transferase 1947A>G polymorphism and smoking initiation, persistent smoking or smoking cessation. Pharmacogenetics 12(3):265–268
Enoch MA, Waheed JF, Harris CR, Albaugh B, Goldman D (2006) Sex differences in the influence of COMT Val158Met on alcoholism and smoking in plains American Indians. Alcohol Clin Exp Res 30(3):399–406
Glover ED, Glover PN, Franzon M, Sullivan CR, Cerullo CC, Howell RM et al (2002) A comparison of a nicotine sublingual tablet and placebo for smoking cessation. Nicotine Tob Res 4(4):441–450
Guo S, da Chen F, Zhou DF, Sun HQ, Wu GY, Haile CN et al (2007) Association of functional catechol O-methyl transferase (COMT) Val108Met polymorphism with smoking severity and age of smoking initiation in Chinese male smokers. Psychopharmacology 190(4):449–456
Hajek P, West R, Foulds J, Nilsson F, Burrows S, Meadow A (1999) Randomized comparative trial of nicotine polacrilex, a transdermal patch, nasal spray, and an inhaler. Arch Intern Med 159(17):2033–2038
Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO (1991) The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict 86(9):1119–1127
Hughes JR (2003) Motivating and helping smokers to stop smoking. J Gen Intern Med 18(12):1053–1057
Johnstone EC, Elliot KM, David SP, Murphy MF, Walton RT, Munafo MR (2007) Association of COMT Val108/158Met genotype with smoking cessation in a nicotine replacement therapy randomized trial. Cancer Epidemiol Biomarkers Prev 16(6):1065–1069
Lachman HM, Papolos DF, Saito T, Yu YM, Szumlanski CL, Weinshilboum RM (1996) Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 6(3):243–250
Lam TH, Abdullah AS, Chan SS, Hedley AJ (2005) Adherence to nicotine replacement therapy versus quitting smoking among Chinese smokers: a preliminary investigation. Psychopharmacology 177(4):400–408
Lee DW, Chan AC, Sze TS, Ko CW, Poon CM, Chan KC et al (2002) Patient-controlled sedation versus intravenous sedation for colonoscopy in elderly patients: a prospective randomized controlled trial. Gastrointest Endosc 56(5):629–632
Lerman C, Niaura R (2002) Applying genetic approaches to the treatment of nicotine dependence. Oncogene 21(48):7412–7420
Mannisto PT, Kaakkola S (1999) Catechol-O-methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors. Pharmacol Rev 51(4):593–628
Mannisto PT, Ulmanen I, Lundstrom K, Taskinen J, Tenhunen J, Tilgmann C et al (1992) Characteristics of catechol O-methyl-transferase (COMT) and properties of selective COMT inhibitors. Prog Drug Res 39:291–350
Munafo MR, Lerman C, Niaura R, Shields AE, Swan GE (2005) Smoking cessation treatment: pharmacogenetic assessment. Curr Opin Mol Ther 7(3):202–208
Munafo MR, Johnstone EC, Guo B, Murphy MF, Aveyard P (2008) Association of COMT Val108/158Met genotype with smoking cessation. Pharmacogenet Genomics 18(2):121–128
Pontieri FE, Tanda G, Orzi F, Di Chiara G (1996) Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs. Nature 382(6588):255–257
Rice ME, Cragg SJ (2004) Nicotine amplifies reward-related dopamine signals in striatum. Nat Neurosci 7(6):583–584
Schmack K, Schlagenhauf F, Sterzer P, Wrase J, Beck A, Dembler T et al (2008) Catechol-O-methyltransferase val158met genotype influences neural processing of reward anticipation. Neuroimage 42(4):1631–1638
Shield AJ, Thomae BA, Eckloff BW, Wieben ED, Weinshilboum RM (2004) Human catechol O-methyltransferase genetic variation: gene resequencing and functional characterization of variant allozymes. Mol Psychiatry 9(2):151–160
Sun HQ, Guo S, Chen DF, Jiang ZN, Liu Y, Di XL, Yang FD, Zhang XY, Kosten TR, Lu L (2009) Family support and employment as predictors of smoking cessation success: a randomized, double-blind, placebo-controlled trial of nicotine sublingual tablets in chinese smokers. Am J Drug Alcohol Abuse 35(3):183–188
Tochigi M, Suzuki K, Kato C, Otowa T, Hibino H, Umekage T et al (2007) Association study of monoamine oxidase and catechol-O-methyltransferase genes with smoking behavior. Pharmacogenet Genomics 17(10):867–872
Tunbridge EM, Huber A, Farrell SM, Stumpenhorst K, Harrison PJ, Walton ME (2012). The Role of Catechol-O-Methyltransferase in Reward Processing and Addiction. CNS Neurol Disord Drug Targets [Epub ahead of print]
Wallstrom M, Nilsson F, Hirsch JM (2000) A randomized, double-blind, placebo-controlled clinical evaluation of a nicotine sublingual tablet in smoking cessation. Addiction 95(8):1161–1171
Yang GH, Ma JM, Liu N, Zhou LN (2005) Smoking and passive smoking in Chinese, 2002. Zhonghua Liu Xing Bing Xue Za Zhi 26(2):77–83
Yang G, Kong L, Zhao W, Wan X, Zhai Y, Chen LC et al (2008) Emergence of chronic non-communicable diseases in China. Lancet 372(9650):1697–1705
Zhang G, Spencer PH, Jin LQ, Cohlberg JA, Beaulieu JM, Julien JP et al (2004) The single neurofilament subunit of lamprey may need another element for filament assembly. J Comp Neurol 471(2):188–200
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.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00702-012-0841-8