Title:Association Between the COMT Val158Met Polymorphism and Antipsychotic Efficacy in Schizophrenia: An Updated Meta-Analysis
Volume: 19
Issue: 10
Author(s): Jingsong Ma, Mingzhe Zhao, Wei Zhou, Mo Li, Cong Huai, Lu Shen, Ting Wang, Hao Wu, Na Zhang, Zhiruo Zhang, Lin He and Shengying Qin*
Affiliation:
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai,China
Keywords:
COMT, Val158Met, polymorphism, antipsychotics, schizophrenia, clinical response.
Abstract:
Background: Catechol-O-methyltransferase (COMT) contributes to the control of synaptic
dopamine (DA) transmission by catalyzing DA degradation in the presynaptic space. The COMT
Val158Met polymorphism (rs4680) substantially alters enzymatic activity and consequently synaptic
DA concentration in the prefrontal cortex and hippocampus. The COMT genotype could, therefore,
exert a major influence on antipsychotic treatment response as many of these agents also target dopaminergic
transmission.
Objective: The present meta-analysis aimed to test a putative relationship between the COMT
Val158Met polymorphism and antipsychotic response across different populations and antipsychotic
types.
Methods: Searches of PubMed, Web of Science, EMBASE, OVID, Google Scholar, and Baidu Scholar
databases yielded 30 peer-reviewed studies published before January 2020 with a pooled total of 6291
participants. The Lipták-Stouffer Z score method for meta-analysis was applied to combine data. The Z
score was also calculated separately for Caucasian and Asian subgroups.
Results: Pooled results indicated a highly significant association between COMT Val158Met and antipsychotic
response (Z = 6.709, P = 9.8 × 10-12). Further, this relationship remained significant in subgroup
analyses of Caucasian patients (Z = 3.180, P = 7.4 × 10-4) and Asian patients (Z = 4.487, P = 3.6
× 10-6).
Conclusion: Pooled evidence supports the hypothesis that the COMT Val158Met polymorphism influences
the antipsychotic response in Caucasian and Asian schizophrenia patient populations. Prediction
of antipsychotic response by patient genotyping may warrant closer consideration in randomized clinical
trials of efficacy.
