The serotonin transporter gene polymorphism is not associated with smoking behavior (original) (raw)

The Pharmacogenomics Journal volume 6, pages 397–400 (2006)Cite this article

Abstract

Nicotine increases serotonin release in the brain and symptoms of nicotine withdrawal may be modulated by diminished serotonergic neurotransmission. The promoter region of the serotonin transporter gene, solute carrier family neurotransmitter transporter member 4 (SLC6A4), contains a functional tandem repeat polymorphism. The long (L) variant is more actively transcribed than the short (S) variant and is associated with a higher serotonin uptake. To investigate the potential role of this polymorphism for smoking behavior, SLC6A4 genotypes were determined in two different studies, the SMOKING GENES case–control study (470 current smokers and 419 subjects who had never smoked) and the cross-sectional Ludwigshafen risk and cardiovascular health (LURIC) study (777 current smokers and 1178 subjects who had never smoked). In the SMOKING GENES case–control study, SLC6A4 genotype frequencies were not statistically different between smokers (LL: 30.9%; LS: 46.8%; SS: 16.4%) and non-smokers (LL: 36.3%; LS: 41.8%; SS: 14.3%; _P_=0.13). Similar results were obtained in the cross-sectional LURIC study (smokers: LL, 36.5%, LS, 45.6%, SS, 17.9%; non-smokers: LL, 33.6%, LS, 48.9%, SS, 17.6%; _P_=0.33). SLC6A4 genotypes were furthermore not associated with Fagerstrom Tolerance Questionnaire score, packyears, number of cigarettes smoked per day or previous attempts to quit smoking. We conclude that the SLC6A4 promoter polymorphism is not a major determinant of smoking behavior in Caucasian.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 6 print issues and online access

$259.00 per year

only $43.17 per issue

Buy this article

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

Abbreviations

DRD:

dopamine receptor

L:

long

LURIC:

Ludwigshafen Risk and Cardiovascular Health

S:

short

SLC6A3:

solute carrier family neurotransmitter transporter member 3

SLC6A4:

solute carrier family neurotransmitter transporter member 4

References

  1. Giordanio JM . Cigarette smoking and vascular disease. In: Sidawy AN, Sumpio BE, De Palma (eds). The Basic Science of Vascular Disease. Futura Publishing: New York, 1997, pp 471–475.
    Google Scholar
  2. True WR, Heath AC, Scherrer JF, Waterman B, Goldberg J, Lin N et al. Genetic and environmenal contributions to smoking. Addiction 1997; 92: 1277–1287.
    Article CAS Google Scholar
  3. Arinami T, Ishiguro H, Onaivi ES . Polymorphisms in genes involved in neurotransmission in relation to smoking. Eur J Pharmacol 2000; 410: 215–226.
    Article CAS Google Scholar
  4. Carmelli D, Swan GE, Robinette D, Fabsitz R . Genetic influence on smoking – a study of male twins. N Engl J Med 1992; 327: 829–833.
    Article CAS Google Scholar
  5. Heath AC, Madden PA, Slutske WS, Martin NG . Personality and the inheritance of smoking behavior: a genetic perspective. Behav Genet 1995; 25: 103–117.
    Article CAS Google Scholar
  6. Schloss P, Williams DC . The serotonin transporter: a primary target for antidepressant drugs. J Psychopharmacol 1998; 12: 115–121.
    Article CAS Google Scholar
  7. Murphy DL, Lerner A, Rudnick G, Lesch KP . Serotonin transporter: gene, genetic disorders, and pharmacogenetics. Mol Interven 2004; 4: 109–123.
    Article CAS Google Scholar
  8. Ramamoorthy S, Bauman AL, Moore KR, Han H, Yang-Feng T, Chang AS et al. Antidepressant and cocain-sensitive human serotonin transporter: molecular cloning, expression and chromosomal localization. Proc Natl Acad Sci USA 1993; 90: 2542–2546.
    Article CAS Google Scholar
  9. Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996; 274: 1527–1531.
    Article CAS Google Scholar
  10. Heils A, Teufel A, Petri S, Stöber G, Riederer P, Bengel D et al. Allelic variation of human serotonin transporter gene expression. J Neurochem 1996; 66: 2621–2624.
    Article CAS Google Scholar
  11. Murakami F, Shimomura T, Kotani K, Ikawa S, Nanba E, Adachi K . Anxiety traits associated with a polymorphism in the serotonin transporter gene regulatory region in the Japanese. J Hum Genet 1999; 44: 15–17.
    Article CAS Google Scholar
  12. Ohara K, Nagai M, Suzuki Y, Ochiai M . Association between anxiety disorders and a functional polymorphism in the serotonin transporter gene. Psychiatry Res 1998; 81: 277–279.
    Article CAS Google Scholar
  13. Ebstein RP, Gritsenko I, Nemanov L, Frisch A, Osher Y, Belmaker RH . No association between the serotonin transporter gene regulatory region polymorphism and the Tridimensional Personality Questionnaire (TPQ) temperament of harm avoidance. Mol Psychiatry 1997; 2: 224–226.
    Article CAS Google Scholar
  14. Jorm AF, Henderson AS, Jacomb PA, Christensen H, Korten AE, Rodgers B et al. An association study of a functional polymorphism of the serotonin transporter gene with personality and psychiatric symptoms. Mol Psychiatry 1998; 3: 449–451.
    Article CAS Google Scholar
  15. Bergen AW, Korczak JF, Weissbecker KA, Goldstein AM . A genome-wide search for loci contributing to smoking and alcoholism. Genet Epidemiol 1999; 1: 55–60.
    Article Google Scholar
  16. Ishikawa H, Ohtsuki T, Ishiguro H, Yamakawa-Kobayashi K, Endo K, Lin YL et al. Association between serotonin transporter gene polymorphism and smoking among Japanese Males. Cancer Epidemiol Biomarkers Prev 1999; 8: 831–833.
    CAS PubMed Google Scholar
  17. Kremer I, Bachner-Melman R, Reshef A, Broude L, Nemanov L, Gritsenko I et al. Association of the serotonin transporter gene with smoking behavior. Am J Psychiatry 2005; 162: 924–930.
    Article Google Scholar
  18. Gerra G, Garofano L, Zaimovic A, Moi G, Branchi B, Bussandri M et al. Association of the serotonin transporter promoter polymorphism with smoking behavior among adolescents. Am J Med Genet B 2004; 135B: 73–78.
    Article Google Scholar
  19. Lerman C, Shields PG, Audrain J, Main D, Cobb B, Boyd NR et al. The role of the serotonin transporter gene in cigarette smoking. Cancer Epidemiol Biomarkers Prev 1998; 7: 253–255.
    CAS PubMed Google Scholar
  20. Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG . Replication validity of genetic association studies. Nat Genet 2001; 29: 306–309.
    Article CAS Google Scholar
  21. Hegele RA . SNP judgments and freedom of association. Arterioscler Thromb Vasc Biol 2002; 22: 1058–1061.
    Article CAS Google Scholar
  22. Campbell H, Rudan I . Interpretation of genetic association studies in complex disease. Pharmacogenomics J 2002; 2: 349–360.
    Article CAS Google Scholar
  23. MacKenzie A, Quinn J . A serotonin transporter gene intron 2 polymorphic region, correlated with affective disorders, has allele-dependent differential enhancer-like properties in the mouse embryo. Proc Natl Acad Sci USA 1999; 96: 15251–15255.
    Article CAS Google Scholar
  24. Heatherton HF, Kozlowski LT, Frecker RC, Fagerstrom KO . The Fagerstrom Test for nicotin dependence: a revision of the Fagerstrom Tolerance Questionaire. Br J Addict 1991; 9: 1119–1127.
    Article Google Scholar
  25. Winkelmann BR, Marz W, Boehm BO, Zotz R, Hager J, Hellstern P et al. Rationale and design of the LURIC study – a resource for functional genomics, pharmacogenomics and long-term prognosis of cardiovascular disease. Pharmacogenomics 2001; 2: 1–73.
    Article Google Scholar

Download references

Acknowledgements

We thank Biomedical scientist Renate Jahrbacher and Biomedical scientist Ernestine Marx-Neuhold for helpful comments and critical evaluation of the manuscript.

Author information

Authors and Affiliations

  1. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, Graz, Austria
    O Trummer, G Grünbacher, M Gutjahr, W März & W Renner
  2. Sonderkrankenanstalt, St Radegund, Austria
    H Köppel
  3. Department of Internal Medicine, Metabolism and Vascular Biology Unit, Medical University Graz, Graz, Austria
    T C Wascher
  4. Department of Cardiac Surgery, Paracelsus Medical University, Salzburg, Austria
    O Stanger
  5. Hugo-Wolf-Gasse 8, Graz, Austria
    S Ramschak-Schwarzer
  6. Division of Endocrinology and Diabetes, Ulm University, Ulm, Germany
    B O Boehm
  7. Cardiology Group, Frankfurt Sachsenhausen, Germany
    B R Winkelmann

Authors

  1. O Trummer
  2. H Köppel
  3. T C Wascher
  4. G Grünbacher
  5. M Gutjahr
  6. O Stanger
  7. S Ramschak-Schwarzer
  8. B O Boehm
  9. B R Winkelmann
  10. W März
  11. W Renner

Corresponding author

Correspondence toW Renner.

Rights and permissions

About this article

Cite this article

Trummer, O., Köppel, H., Wascher, T. et al. The serotonin transporter gene polymorphism is not associated with smoking behavior.Pharmacogenomics J 6, 397–400 (2006). https://doi.org/10.1038/sj.tpj.6500389

Download citation

Keywords

This article is cited by