Skip to main content

Advertisement

SpringerLink
Log in

Association of functional catechol O-methyl transferase (COMT) Val108Met polymorphism with smoking severity and age of smoking initiation in Chinese male smokers

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Catechol-O-methyltransferase (COMT) is an enzyme involved in the degradation and inactivation of the neurotransmitter dopamine, which is important in mediating drug reward such as nicotine in tobacco smoke. Different COMT alleles encode enzyme whose activity varies from three- to fourfold that may affect dopamine levels and alter subjective effects of nicotine. Recent evidence also suggests that a COMT polymorphism may be especially important in determining an individual’s predisposition to developing nicotine dependence.

Subjects and methods

We studied the COMT Val108Met polymorphism in a male population of 203 current smokers, 66 former smokers, and 102 non-smokers. The age-adjusted odds ratios were estimated by multiple logistic regression models.

Results

The results showed no significant association of the COMT Val108Met with initiation, persistent smoking, or smoking cessation. However, current smokers with the Met allele had significantly higher Fagerstrom Test for Nicotine Dependence scores (7.5 ± 2.1 vs 6.8 ± 1.8, p = 0.018) and started smoking significantly earlier (18.4 ± 4.9 vs 20.1 ± 5.9 years, p = 0.036).

Conclusions

These results suggest that the COMT Val108Met polymorphism may not influence smoking status in a Chinese male population but may influence the age at which smoking started and smoking severity among smokers. However, the findings must be regarded as preliminary because of the relatively small sample size and marginal associations and should be replicated in a larger cohort.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • 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 31:675–684

    Article  PubMed  CAS  Google Scholar 

  • Chen J, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S, Kolachana BS, Hyde TM, Herman MM, Apud J, Egan MF, Kleinman JE, Weinberger DR (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 75:807–821

    Article  PubMed  CAS  Google Scholar 

  • Colilla S, Lerman C, Shields PG, Jepson C, Rukstalis M, Berlin J, DeMichele A, Bunin G, Strom BL, Rebbeck TR (2005) Association of catechol-O-methyltransferase with smoking cessation in two independent studies of women. Pharmacogenet Genomics 15:393–398

    Article  PubMed  CAS  Google Scholar 

  • David SP, Johnstone E, Griffiths SE, Murphy M, Yudkin P, Mant D, Walton R (2002) No association between functional catechol O-methyl transferase 1947A>G polymorphism and smoking initiation, persistent smoking or smoking cessation. Pharmacogenetics 12:265–268

    Article  PubMed  CAS  Google Scholar 

  • Fagerstrom KO (1978) Measuring degree of physical dependence to tobacco smoking with reference to individualization of treatment. Addict Behav 3:235–241

    Article  PubMed  CAS  Google Scholar 

  • He J, Gu D, Wu X, Reynolds K, Duan X, Yao C, Wang J, Chen CS, Chen J, Wildman RP, Klag MJ, Whelton PK (2005) Major causes of death among men and women in China. N Engl J Med 353:1124–1234

    Article  PubMed  CAS  Google Scholar 

  • Hu TW and Tsai YW (2000) Cigarette consumption in rural China: survey results from 3 provinces. Am J Public Health 90:1785–1787

    Article  PubMed  CAS  Google Scholar 

  • Hutchison KE, LaChance H, Niaura R, Bryan A, Smolen A (2002) The DRD4 VNTR polymorphism influences reactivity to smoking cues. J Abnorm Psychology 111:134–143

    Article  Google Scholar 

  • Ishikawa H, Ohtsuki T, Ishiguro H, Yamakawa-Kobayashi K, Endo K, Lin YL, Yanagi H, Tsuchiya S, Kawata K, Hamaguchi H, Arinami T (1999) Association between serotonin transporter gene polymorphism and smoking among Japanese males. Cancer Epidemiol Biomark Prev 8:831–833

    CAS  Google Scholar 

  • Ito H, Hamajima N, Matsuo K, Okuma K, Sato S, Ueda R, Tajima K (2003) Monoamine oxidase polymorphisms and smoking behaviour in Japanese. Pharmacogenetics 13:73–79

    Article  PubMed  CAS  Google Scholar 

  • Jorm AF, Henderson AS, Jacomb PA, Christensen H, Korten AE, Rodgers B, Tan X, Easteal S (2000) Association of smoking and personality with a polymorphism of the dopamine transporter gene: results from a community survey. Am J Med Genet 96:331–334

    Article  PubMed  CAS  Google Scholar 

  • Kendler KS, Neale MC, Sullivan P, Corey LA, Gardner CO, Prescott CA (1999) A population-based twin study in women of smoking initiation and nicotine dependence. Psychol Med 29:299–308

    Article  PubMed  CAS  Google Scholar 

  • 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 6:243–250

    Article  PubMed  CAS  Google Scholar 

  • Lee WC (2003) Detecting population stratification using a panel of single nucleotide polymorphisms. Int J Epidemiol 32:1120

    Article  PubMed  Google Scholar 

  • Li MD (2003) The genetics of smoking related behavior: a brief review. Am J Med Sci 326:168–173

    Article  PubMed  Google Scholar 

  • Maes HH, Sullivan PF, Bulik CM, Neale MC, Prescott CA, Eaves LJ, Kendler KS (2004) A twin study of genetic and environmental influences on tobacco initiation, regular tobacco use and nicotine dependence. Psychol Med 34:1251–1261

    Article  PubMed  Google Scholar 

  • Manly KF (2005) Conventional P-values fail to assure reproducibility for genetic association tests. Trends Genet 21:268–269

    Article  PubMed  CAS  Google Scholar 

  • Mannisto PT, Ulmanen I, Lundstrom K, Taskinen J, Tenhunen J, Tilgmann C, Kaakkola S (1992) Characteristics of catechol O-methyl-transferase (COMT) and properties of selective COMT inhibitors. Prog Drug Res 39:291–350

    PubMed  CAS  Google Scholar 

  • Mannisto PT, Kaakkola S (1999) Catechol-O-methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors. Pharmacol Rev 51:593–628

    PubMed  CAS  Google Scholar 

  • McKinney EF, Walton RT, Yudkin P, Fuller A, Haldar NA, Mant D, Murphy M, Welsh KI, Marshall SE (2000) Association between polymorphisms in dopamine metabolic enzymes and tobacco consumption in smokers. Pharmacogenetics 10:483–491

    Article  PubMed  CAS  Google Scholar 

  • Monden CW (2004) Current or lifetime smoking? Consequences for explaining educational inequalities in self-reported health. Prev Med 39:19–26

    Article  PubMed  Google Scholar 

  • Munafo M, Clark T, Johnstone E, Murphy M, Walton R (2004) The genetic basis for smoking behavior: a systematic review and meta-analysis. Nicotine Tob Res 6:583–597

    Article  PubMed  CAS  Google Scholar 

  • Paavola M, Vartiainen E, Haukkala A (2004) Smoking, alcohol use, and physical activity: a 13-year longitudinal study ranging from adolescence into adulthood. J Adolesc Health 35:238–244

    PubMed  Google Scholar 

  • 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 382:255–257

    Article  PubMed  CAS  Google Scholar 

  • Redden DT, Allison DB (2006) The effect of assortative mating upon genetic association studies: spurious associations and population substructure in the absence of admixture. Behav Genet (in press)

  • Robinson TE, Berridge KC (2003) Addiction. Annu Rev Psychol 54:25–53

    Article  PubMed  Google Scholar 

  • Rossing MA (1998) Genetic influences on smoking: candidate genes. Environ Health Perspect 106:231–238

    PubMed  CAS  Google Scholar 

  • 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 9:151–160

    Article  PubMed  CAS  Google Scholar 

  • Singleton AB, Thomson JH, Morris CM, Court JA, Lloyd S, Cholerton S (1998) Lack of association between the dopamine D2 receptor gene allele DRD2*A1 and cigarette smoking in a United Kingdom population. Pharmacogenetics 8:125–128

    Article  PubMed  CAS  Google Scholar 

  • True WR, Heath AC, Scherrer JF, Waterman B, Goldberg J, Lin N, Eisen SA, Lyons MJ, Tsuang MT (1997) Genetic and environmental contributions to smoking. Addiction 92:1277–1287

    Article  PubMed  CAS  Google Scholar 

  • Vandenbergh DJ, Rodriguez LA, Miller IT, Uhl GR, Lachman HM (1997) High-activity catechol-O-methyltransferase allele is more prevalent in polysubstance abusers. Am J Med Genet 74:439–442

    Article  PubMed  CAS  Google Scholar 

  • Yang G, Fan LMS, Tan J, Qi G, Zhang Y, Samet JM (1999). Smoking in China: findings of the 1996 National Prevalence Survey. JAMA 282:1247–1253

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This study was funded by the Stanley Medical Institute Foundation 03T-459 (XYZ) and the Department of Veterans Affairs, VISN 1, Mental Illness Research, Education and Clinical Center (MIRECC), and National Institute on Drug Abuse K05-DA0454 and P50-DA18827 (TRK).

Author information

Authors and Affiliations

  1. Institute of Mental Health, Peking University, Beijing, 100083, China

    Song Guo, Dong Feng Zhou & Xiang Yang Zhang

  2. Department of Epidemiology and Statistics, Peking University School of Public Health, 38 Xueyuan Road, Haidian District, Beijing, 100083, China

    Da Fang Chen

  3. National Drug Dependence Treatment Center, Beijing Anding Hospital Affiliated Capital University of Medical Sciences, Beijing, China

    Song Guo

  4. Center for Biological Psychiatry, Beijing Huilongguan Hospital, Beijing, China

    Hong Qiang Sun & Xiang Yang Zhang

  5. Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, VA Medical Center, Research Building 109, Room 130, 2002 Holcombe Boulevard, Houston, TX, 77030, USA

    Gui Ying Wu, Colin N. Haile, Therese A. Kosten, Thomas R. Kosten & Xiang Yang Zhang

Authors
  1. Song Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Da Fang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dong Feng Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hong Qiang Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gui Ying Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Colin N. Haile
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Therese A. Kosten
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Thomas R. Kosten
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xiang Yang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Da Fang Chen, Dong Feng Zhou or Xiang Yang Zhang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guo, S., Chen, D.F., Zhou, D.F. et al. Association of functional catechol O-methyl transferase (COMT) Val108Met polymorphism with smoking severity and age of smoking initiation in Chinese male smokers. Psychopharmacology 190, 449–456 (2007). https://doi.org/10.1007/s00213-006-0628-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-006-0628-4

Keywords

Search

Navigation