Evidence map›Paper›PMID 22700043›Full record

ArticlePsychopharmacology2012

Outcome definitions and clinical predictors influence pharmacogenetic associations between HTR3A gene polymorphisms and response to clozapine in patients with schizophrenia.

A P Rajkumar, B Poonkuzhali, A Kuruvilla, A Srivastava, M Jacob, K S Jacob

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Article in Psychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

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9citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

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  5. Tapping into 5-HTInternational journal of molecular sciences · 2021
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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

6 authors.

A P RajkumarDepartment of Psychiatry, Christian Medical College, Vellore 632002, India.
B Poonkuzhali
A Kuruvilla
A Srivastava
M Jacob
K S Jacob

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

rationalePharmacogenetics of schizophrenia has not yet delivered anticipated clinical dividends. Clinical heterogeneity of schizophrenia contributes to the poor replication of the findings of pharmacogenetic association studies. Functionally important HTR3A gene single-nucleotide polymorphisms (SNPs) were reported to be associated with response to clozapine.

objectiveThe aim of this study was to investigate how the association between HTR3A gene SNP and response to clozapine is influenced by various clinical predictors and by differing outcome definitions in patients with treatment-resistant schizophrenia (TRS).

methodsWe recruited 101 consecutive patients with TRS, on stable doses of clozapine, and evaluated their HTR3A gene SNP (rs1062613 and rs2276302), psychopathology, and serum clozapine levels. We assessed their socio-demographic and clinical profiles, premorbid adjustment, traumatic events, cognition, and disability using standard assessment schedules. We evaluated their response to clozapine, by employing six differing outcome definitions. We employed appropriate multivariate statistics to calculate allelic and genotypic association, accounting for the effects of various clinical variables.

resultsT allele of rs1062613 and G allele of rs2276302 were significantly associated with good clinical response to clozapine (p = 0.02). However, varying outcome definitions make these associations inconsistent. rs1062613 and rs2276302 could explain only 13.8 % variability in the responses to clozapine, while combined clinical predictors and HTR3A pharmacogenetic association model could explain 38 % variability.

conclusionsWe demonstrated that the results of pharmacogenetic studies in schizophrenia depend heavily on their outcome definitions and that combined clinical and pharmacogenetic models have better predictive values. Future pharmacogenetic studies should employ multiple outcome definitions and should evaluate associated clinical variables.

Indexed as

Polymorphism, Single NucleotideAdultAntipsychotic AgentsCase-Control StudiesChi-Square DistributionClozapineCross-Sectional StudiesDrug ResistanceFemaleGene FrequencyGenotypeHumansLogistic ModelsMaleMiddle AgedMultivariate AnalysisAntipsychotic AgentsClozapineHTR3A protein, humanReceptors, Serotonin, 5-HT3Serotonin Antagonists

Identifiers

PMID22700043

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.