Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

The association between HTR2C polymorphisms and obesity in psychiatric patients using antipsychotics: a cross-sectional study

The Pharmacogenomics Journal volume 7, pages 318–324 (2007)Cite this article

Abstract

The use of antipsychotics is associated with an increased risk of obesity. This consideration makes it important to search for determinants that can predict the risk for antipsychotic-induced obesity. In this cross-sectional study, we investigated whether polymorphisms in the HTR2C gene were associated with obesity (body mass index >30 kg/m2) in patients using antipsychotics. We examined polymorphisms in the promoter region of the HTR2C gene ((HTR2C:c.1–142948(GT)n, rs3813928 (−997 G/A), rs3813929 (−759 C/T), rs518147 (−697 G/C)) and an intragenic polymorphism (rs1414334:C>G). The results of the logistic regression were expressed as adjusted odds ratios (OR). In total, we included 127 patients mainly diagnosed with schizophrenia or schizoaffective disorder (89%). The results indicate that a combined genotype carrying the variant HTR2C:c.1–142948(GT)n 13 repeat allele, the common allele rs3813929 C, the variant allele rs518147 C and the variant allele rs1414334 C is significantly related to an increased risk of obesity (OR 3.71 (95% confidence interval: 1.24–11.12)).

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1

Similar content being viewed by others

References

  1. Allison DB, Casey DE . Antipsychotic-induced weight gain: a review of the literature. J Clin Psychiatry 2001; 62 (Suppl 7): 22–31.

    CAS  PubMed  Google Scholar 

  2. Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH . The disease burden associated with overweight and obesity. JAMA 1999; 282: 1523–1529.

    Article  CAS  Google Scholar 

  3. Allison DB, Fontaine KR, Manson JE, Stevens J, VanItallie TB . Annual deaths attributable to obesity in the United States. JAMA 1999; 282: 1530–1538.

    Article  CAS  Google Scholar 

  4. Muller DJ, Muglia P, Fortune T, Kennedy JL . Pharmacogenetics of antipsychotic-induced weight gain. Pharmacol Res 2004; 49: 309–329.

    Article  CAS  Google Scholar 

  5. Hugenholtz GW, Heerdink ER, Meijer WE, Stolker JJ, Egberts AC, Nolen WA . Reasons for switching between antipsychotics in daily clinical practice. Pharmacopsychiatry 2005; 38: 122–124.

    Article  CAS  Google Scholar 

  6. Yuan X, Yamada K, Ishiyama-Shigemoto S, Koyama W, Nonaka K . Identification of polymorphic loci in the promoter region of the serotonin 5-HT2C receptor gene and their association with obesity and type II diabetes. Diabetologia 2000; 43: 373–376.

    Article  CAS  Google Scholar 

  7. Reynolds GP, Zhang ZJ, Zhang XB . Association of antipsychotic drug-induced weight gain with a 5-HT2C receptor gene polymorphism. Lancet 2002; 359: 2086–2087.

    Article  CAS  Google Scholar 

  8. Reynolds GP, Zhang Z, Zhang X . Polymorphism of the promoter region of the serotonin 5-HT(2C) receptor gene and clozapine-induced weight gain. Am J Psychiatry 2003; 160: 677–679.

    Article  Google Scholar 

  9. Templeman LA, Reynolds GP, Arranz B, San L . Polymorphisms of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a first-episode psychosis. Pharmacogenet Genomics 2005; 15: 195–200.

    Article  CAS  Google Scholar 

  10. Ellingrod VL, Perry PJ, Ringold JC, Lund BC, Bever-Stille K, Fleming F et al. Weight gain associated with the −759C/T polymorphism of the 5HT2C receptor and olanzapine. Am J Med Genet B 2005; 134: 76–78.

    Article  Google Scholar 

  11. Miller dD, Ellingrod VL, Holman TL, Buckley PF, Arndt S . Clozapine-induced weight gain associated with the 5HT2C receptor −759C/T polymorphism. Am J Med Genet B 2005; 133: 97–100.

    Article  Google Scholar 

  12. Theisen FM, Hinney A, Bromel T, Heinzel-Gutenbrunner M, Martin M, Krieg JC et al. Lack of association between the −759C/T polymorphism of the 5-HT2C receptor gene and clozapine-induced weight gain among German schizophrenic individuals. Psychiatr Genet 2004; 14: 139–142.

    Article  Google Scholar 

  13. Ellingrod VL, Miller D, Ringold JC, Perry PJ . Distribution of the serotonin 2C (5HT2C) receptor gene −759C/T polymorphism in patients with schizophrenia and normal controls. Psychiatr Genet 2004; 14: 93–95.

    Article  Google Scholar 

  14. Tsai SJ, Hong CJ, Yu YW, Lin CH . 759C/T genetic variation of 5HT(2C) receptor and clozapine-induced weight gain. Lancet 2002; 360: 1790.

    Article  Google Scholar 

  15. Basile VS, Masellis M, De Luca V, Meltzer HY, Kennedy JL . 759C/T genetic variation of 5HT(2C) receptor and clozapine-induced weight gain. Lancet 2002; 360: 1790–1791.

    Article  Google Scholar 

  16. Reynolds GP, Templeman LA, Zhang ZJ . The role of 5-HT2C receptor polymorphisms in the pharmacogenetics of antipsychotic drug treatment. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29: 1021–1028.

    Article  CAS  Google Scholar 

  17. Pooley EC, Fairburn CG, Cooper Z, Sodhi MS, Cowen PJ, Harrison PJ . A 5-HT2C receptor promoter polymorphism (HT). Am J Med Genet B 2004; 126: 124–127.

    Article  Google Scholar 

  18. McCarthy S, Mottagui-Tabar S, Mizuno Y, Sennblad B, Hoffstedt J, Arner P et al. Complex HTR2C linkage disequilibrium and promoter associations with body mass index and serum leptin. Hum Genet 2005; 117: 545–557.

    Article  CAS  Google Scholar 

  19. Perneger TV . What's wrong with Bonferroni adjustments. BMJ 1998; 316: 1236–1238.

    Article  CAS  Google Scholar 

  20. Blin O, Micallef J . Antipsychotic-associated weight gain and clinical outcome parameters. J Clin Psychiatry 2001; 62 (Suppl 7): 11–21.

    CAS  PubMed  Google Scholar 

  21. Ronaghi M, Uhlen M, Nyren P . A sequencing method based on real-time pyrophosphate. Science 1998; 281: 363–365.

    Article  CAS  Google Scholar 

  22. Pacey-Miller T, Henry R . Single-nucleotide polymorphism detection in plants using a single-stranded pyrosequencing protocol with a universal biotinylated primer. Anal Biochem 2003; 317: 166–170.

    Article  Google Scholar 

  23. Anonymous. Anatomical Therapeutic Chemical (ATC) Classification Index: Including Defined Daily Doses (DDDs) for Plain Substances. World Health Organization: Oslo, Norway, 1997.

  24. Vanina Y, Podolskaya A, Sedky K, Shahab H, Siddiqui A, Munshi F et al. Body weight changes associated with psychopharmacology. Psychiatr Serv 2002; 53: 842–847.

    Article  Google Scholar 

  25. Wirshing DA, Boyd JA, Meng LR, Ballon JS, Marder SR, Wirshing WC . The effects of novel antipsychotics on glucose and lipid levels. J Clin Psychiatry 2002; 63: 856–865.

    Article  CAS  Google Scholar 

  26. Barrett JC, Fry B, Maller J, Daly MJ . Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005; 21: 263–265.

    Article  CAS  Google Scholar 

  27. Maldonado G, Greenland S . Simulation study of confounder-selection strategies. Am J Epidemiol 1993; 138: 923–936.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was kindly supported financially by the Mental Health Services Drenthe, Assen, The Netherlands and the Arijan Porsius foundation, Utrecht, The Netherlands. We thank Cees Slooff and Wim van Oven for establishing initial contacts and stimulating discussions and Annet Derks for careful assistance. We are thankful for the help of Marc Bijen in setting up and carrying out the genotyping.

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacoepidemiology, Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science,

    H Mulder & A C G Egberts

  2. Utrecht University, Utrecht, The Netherlands

    H Mulder & A C G Egberts

  3. Department of Clinical Pharmacy, Wilhelmina Hospital Assen, Assen, The Netherlands

    H Mulder

  4. Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    B Franke & H Scheffer

  5. Department of Clinical Pharmacy, Martini Hospital Groningen, Groningen, The Netherlands

    A Aart van der – Beek van der

  6. Department of Psychotic Disorders, Mental Health Services Drenthe, Assen, The Netherlands

    J Arends

  7. Mental Health Services Drenthe, Assen, The Netherlands

    F W Wilmink

  8. Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands

    A C G Egberts

Authors
  1. H Mulder
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B Franke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Aart van der – Beek van der
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J Arends
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. F W Wilmink
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A C G Egberts
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H Scheffer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A C G Egberts.

Additional information

Duality of Interest

None declared.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mulder, H., Franke, B., Aart van der – Beek van der, A. et al. The association between HTR2C polymorphisms and obesity in psychiatric patients using antipsychotics: a cross-sectional study. Pharmacogenomics J 7, 318–324 (2007). https://doi.org/10.1038/sj.tpj.6500422

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.tpj.6500422

Keywords

This article is cited by

Search

Advanced search

Quick links