Possible association of the pro-melanin-concentrating hormone gene with a Greater body mass index as a side effect of the antipsychotic olanzapine

Y. C. Chagnon, Alexandre Bureau, D. Gendron, R. H. Bouchard, C. Mérette, M. A. Roy, M. Maziade

Research output: Contribution to journalArticle

Abstract

Following our report of a linkage at 12q24 with a phenotype of obesity under antipsychotics, we tested the pro-melanin-concentrating hormone (PMCH) candidate gene for a possible association in humans with the body mass index (BMI; kg/m2) in unrelated schizophrenic patients (SZ) receiving antipsychotics (N = 300) and in controls (CTL; N = 150). Subjects were classified in obese (OB) (BMI ≥ 30 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and normal weight (BMI < 25 kg/m2) groups. Single nucleotide polymorphisms (SNP) rs7973796 and rs11111201, located 5′ at -4.5 kb and 3′ at +1.8 kb, respectively, of PMCH were genotyped. Interaction effects of genotypes and antipsychotic treatment on BMI were tested in a covariance analysis with age and gender as covariates. Interaction effects on the prevalence of obesity were tested in a logistic regression analysis. For subjects under 50 years, the effect of the rs7973796 genotype on BMI differed between the SZ patients taking olanzapine and CTL group (interaction P = 0.025). Olanzapine-treated SZ patients carrying the ancestral homozygote genotype showed a higher BMI for rs7973796 (P = 0.016 with the LSMeans t-test) than the variant homozygotes. Accordingly, the ORs for obesity associated with rs7973796 genotypes differed in the SZ patients taking olanzapine compared to the CTL group (interaction P = 0.0094). The G allele was associated with an increase in the odds of obesity in SZ patients taking olanzapine. No association was observed for those over 50 years, or for rs11111201. These results suggest that the common allele of PMCH rs7973796 may be associated with a greater BMI in olanzapine-treated SZ patients.

Original languageEnglish (US)
Pages (from-to)1063-1069
Number of pages7
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume144
Issue number8
DOIs
StatePublished - Dec 5 2007
Externally publishedYes

Fingerprint

olanzapine
Antipsychotic Agents
Body Mass Index
Genes
Obesity
Genotype
Homozygote
melanin-concentrating hormone precursors
Alleles

Keywords

  • Drugs
  • Obesity
  • Pharmacogenetics
  • Pharmacogenomics
  • Schizophrenia
  • Side-effects
  • Weight

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Possible association of the pro-melanin-concentrating hormone gene with a Greater body mass index as a side effect of the antipsychotic olanzapine. / Chagnon, Y. C.; Bureau, Alexandre; Gendron, D.; Bouchard, R. H.; Mérette, C.; Roy, M. A.; Maziade, M.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 144, No. 8, 05.12.2007, p. 1063-1069.

Research output: Contribution to journalArticle

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