Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene

N. I. Chowdhury, A. K. Tiwari, R. P. Souza, C. C. Zai, S. A. Shaikh, S. Chen, F. Liu, J. A. Lieberman, H. Y. Meltzer, A. K. Malhotra, J. L. Kennedy, D. J. Müller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Antipsychotic-induced weight gain (AIWG) may result in the metabolic syndrome in schizophrenia (SCZ) patients. Downstream variants of the melanocortin-4 receptor (MC4R) gene have been associated with obesity in various populations. Thus, we examined single-nucleotide polymorphisms (SNPs) in the MC4R region for association with AIWG in SCZ patients. Four SNPs (rs2229616, rs17782313, rs11872992 and rs8087522) were genotyped in 224 patients who underwent treatment for SCZ and were evaluated for AIWG for up to 14 weeks. We compared weight change (%) across genotypic groups using analysis of covariance for three SNPs (r 2 ≤0.8). European-ancestry patients who were rs8087522 A-allele carriers (AG+AA) on clozapine gained significantly more weight than non-carriers (P=0.027, n=69). These observations were marginal after correction for multiple testing. We performed in vitro electrophoretic mobility-shift assay that suggested that the presence of the A-allele may create a transcription factor-binding site. Further investigation is warranted for both these exploratory findings.

Original languageEnglish (US)
Pages (from-to)272-279
Number of pages8
JournalPharmacogenomics Journal
Volume13
Issue number3
DOIs
StatePublished - Jun 1 2013

Keywords

  • Association study
  • MC4R
  • clozapine
  • electrophoretic mobility-shift assays
  • pharmacogenetics
  • weight gain

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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