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MC4R rs489693: a clinical risk factor for second generation antipsychotic-related weight gain?

Fabian Czerwensky1, Stefan Leucht, Werner Steimer

  • 1Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str 22 81675 München, Germany.

The International Journal of Neuropsychopharmacology
|August 8, 2013
PubMed

Insights

The rs489693 A-allele near the melanocortin 4 receptor gene is linked to increased weight gain in patients taking second-generation antipsychotics (SGAs). This finding suggests a genetic risk factor for this common side effect.

Area of Science:

  • Pharmacogenetics
  • Neuroscience
  • Genetics

Background:

  • Weight gain is a frequent and limiting adverse effect of second-generation antipsychotics (SGAs).
  • The human melanocortin 4 receptor (MC4R) gene is a potential factor influencing SGA-induced weight gain.
  • A genome-wide association study identified the rs489693 polymorphism near MC4R as associated with SGA-related weight gain.

Purpose of the Study:

  • To replicate the association between the rs489693 polymorphism and SGA-related weight gain in an independent study population.
  • To investigate the rs489693 polymorphism as a potential genetic predictor of weight gain in patients treated with SGAs.

Main Methods:

  • A naturalistic study involving 341 Caucasian inpatients treated with SGAs (olanzapine, clozapine, risperidone, paliperidone, quetiapine, amisulpride).
  • Genotyping for the rs489693 polymorphism.
  • Analysis of weight changes after 4 weeks of treatment using analysis of covariance.

Main Results:

  • Patients homozygous for the rs489693 A-allele showed a 2.2 times higher weight increase (+2.2 kg) compared to CC-genotype carriers (+1 kg) (p = 0.039).
  • A stronger effect was observed in a subpopulation without weight-gain-inducing co-medication (factor 3.1, +2.8 kg, p = 0.044).
  • The A-allele also showed a significant effect in first-episode patients (factor 2.7, +2.7 kg, p = 0.017).

Conclusions:

  • The rs489693 A-allele is confirmed as a potential risk factor for weight gain associated with second-generation antipsychotic treatment.
  • This genetic marker may help identify individuals at higher risk for SGA-induced weight gain.
  • Further research is warranted to explore the clinical utility of rs489693 genotyping in personalized antipsychotic treatment strategies.

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