The HTR2A rs6311 and rs6313 polymorphisms and atypical antipsychotics response in schizophrenia: a scoping review

30/07/2026

AI Summary

HTR2A rs6311 A allele often associates with better AAP response, whereas the G allele associates with poorer or absent response.
HTR2A rs6313 shows heterogeneous associations; C allele linked to poorer response in some studies, T allele to improved response in others.
Overall HTR2A variants may contribute to AAP response variability but current evidence is insufficient for clinical application; adequately powered, well designed studies are required.

AI Summary

The Joanna Briggs Institute and Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews criteria were followed in this scoping review to map the available data on the association between HTR2A polymorphisms and outcomes.

Several studies reported that the rs6311 A allele was more frequently associated with improved treatment response, whereas the G allele was linked to poorer or absent response.

In contrast, rs6313 exhibited heterogeneous patterns, with some studies reporting poorer response associated with the C allele and others reporting improved response associated with the T allele.

Basic summary

Pharmacogenet Genomics. 2026 Sep 1;36(5):185-194. doi: 10.1097/FPC.0000000000000600. Epub 2026 Jul 28.

ABSTRACT

The HTR2A polymorphisms rs6311 (A-1438G) and rs6313 (T102C) have been thoroughly studied for their impact on atypical antipsychotics (AAPs) responsiveness in schizophrenia. However, the results remain inconsistent owing to the complex genetic and pharmacodynamic interactions. The Joanna Briggs Institute and Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews criteria were followed in this scoping review to map the available data on the association between HTR2A polymorphisms and outcomes. We identified 28 studies published before May 2025. Several studies reported that the rs6311 A allele was more frequently associated with improved treatment response, whereas the G allele was linked to poorer or absent response. In contrast, rs6313 exhibited heterogeneous patterns, with some studies reporting poorer response associated with the C allele and others reporting improved response associated with the T allele. This variability across studies likely reflects differences related to specific AAPs, as well as variations in study design and outcome definitions, rather than population or ethnicity-specific biological effects. Overall, HTR2A variants may contribute to interindividual variability in response to AAPs in schizophrenia. However, the current evidence remains insufficient for clinical application and requires further validation in well-designed and adequately powered studies.

PMID:42531509 | DOI:10.1097/FPC.0000000000000600

Document this CPD