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Possible association of the pro‐melanin‐concentrating hormone gene with a greater body mass index as a side effect of the antipsychotic olanzapine
Author(s) -
Chag Y.C.,
Bureau A.,
Gendron D.,
Bouchard R.H.,
Mérette C.,
Roy M.A.,
Maziade M.
Publication year - 2007
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30554
Subject(s) - olanzapine , body mass index , overweight , odds ratio , obesity , medicine , genotype , single nucleotide polymorphism , allele , endocrinology , genetics , biology , schizophrenia (object oriented programming) , psychiatry , gene
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/m 2 ) in unrelated schizophrenic patients (SZ) receiving antipsychotics (N = 300) and in controls (CTL; N = 150). Subjects were classified in obese (OB) (BMI ≥ 30 kg/m 2 ), overweight (25 ≤ BMI < 30 kg/m 2 ), and normal weight (BMI < 25 kg/m 2 ) groups. Single nucleotide polymorphisms (SNP) rs7973796 and rs201, 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 rs201. These results suggest that the common allele of PMCH rs7973796 may be associated with a greater BMI in olanzapine‐treated SZ patients. © 2007 Wiley‐Liss, Inc.