Genetic association of the rs17782313 polymorphism with antipsychotic-induced weight gain.

Schreyer, Korbinian Felix; Leucht, Stefan; Heres, Stephan; Steimer, Werner

doi:10.1007/s00213-023-06331-9

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Title:: Genetic association of the rs17782313 polymorphism with antipsychotic-induced weight gain.
Document type:: Article; Randomized Controlled Trial; Multicenter Study; Journal Article
Author(s):: Schreyer, Korbinian Felix; Leucht, Stefan; Heres, Stephan; Steimer, Werner
Abstract:: RATIONALE: Weight gain is a frequent side effect of treatment with SGAs (second-generation antipsychotics) and a leading cause for nonadherence. Several candidate genes have been identified that could influence the amount of AIWG (antipsychotic-induced weight gain). The polymorphism rs17782313 near the MC4R (human melanocortin 4 receptor gene) was strongly associated with obesity in a large scale GWAS (genome wide association study), yet previous studies investigating its impact on AIWG did not lead to a definite conclusion regarding its effect. In particular, they were all relatively short and had a naturalistic design. OBJECTIVE: We therefore examined the influence of the rs17782313 polymorphism on SGA-related weight gain. METHODS: Participants of a multicenter randomized, controlled, double-blind study comparing two treatment strategies in individuals with schizophrenia or schizoaffective disorder were genotyped using a rapid-cycle polymerase chain reaction. Up to 252 individuals completed the first 2 weeks (phase I), 212 the entire 8 weeks (hence 'completers'). Patients received either amisulpride or olanzapine or both consecutively. Thirty-seven had their first episode. Weight gain occurring in different genotypes was statistically compared and confounding factors were adjusted by stepwise multiple linear regression. A correction for multiple testing was included. RESULTS: Within 212 'completers', carriers of the C allele had a higher absolute weight gain than those homozygous for the T allele (2.6 kg vs. 1.2 kg), though this observation was not significant (P = 0.063). In the amisulpride subpopulation, this association appeared stronger and reached significance (2.5 kg vs. 0.7 kg, P = 0.043), though failed to remain significant after correction for multiple testing. A stepwise multiple linear regression showed a significant association in both the whole study population (P < 0.001) and the amisulpride subpopulation (P < 0.001). CONCLUSION: Our results indicate that the rs17782313 polymorphism might influence antipsychotic-induced weight gain and therefore confirm some of the earlier conclusions.
Journal title abbreviation:: Psychopharmacology (Berl)
Year:: 2023
Journal volume:: 240
Journal issue:: 4
Pages contribution:: 899-908
Fulltext / DOI:: doi:10.1007/s00213-023-06331-9
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/36757449
Print-ISSN:: 0033-3158
TUM Institution:: Institut für Klinische Chemie und Pathobiochemie (Prof. Ruland)
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