4.2 Article

Polymorphisms of the HTR2C gene and antipsychotic-induced weight gain: an update and meta-analysis

Journal

PHARMACOGENOMICS
Volume 11, Issue 11, Pages 1561-1571

Publisher

FUTURE MEDICINE LTD
DOI: 10.2217/PGS.10.123

Keywords

5-HT2C receptor; antipsychotics; genetics; HTR2C; meta-analysis; weight gain

Funding

  1. CIHR [MOP-15007, 185189]
  2. NARSAD
  3. Prentiss Foundation
  4. Ritter Foundation
  5. Hintz family
  6. Peterson Family
  7. Bebensee fellowship
  8. [MH41468]

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Aims: This study aims to test for possible associations between the gene coding for the 5-HT2C receptor and antipsychotic-induced weight gain. Materials & methods: Four HTR2C polymorphisms (rs498207, C-759T, G-697C and Ser23Cys) were investigated in our sample of 205 chronic schizophrenia patients. Results: Significant over-representation of the C-G-Cys23 haplotype in patients with weight gain (OR: 1.93; 95% CI: 1.04-3.56; p = 0.0015) was found. Similarly, haplotype analyses of percentage weight change were also significant (p = 0.029) for the C-G-Cys23 haplotype associated with the highest average percent weight gain. Observations in the polymorphisms are consistent with previous studies. An updated meta-analysis of nine previous studies plus our current sample suggest that the -759C allele is associated with antipsychotic-induced weight gain. Conclusion: Additional studies, including the resequencing of the region surrounding the HTR2C promoter, and functional studies of the promoter polymorphisms, may elucidate the mechanism underlying this genetic association.

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