How do genetic variants in the COMT gene influence the treatment response to raloxifene in schizophrenia-spectrum disorders (SSD)?

Label:chem

Topic
The COMT gene encodes catechol-O-methyltransferase, an enzyme that degrades catecholamines and catechol-estrogens. Variations in the COMT gene have been associated with differences in antipsychotic drug response and cognitive functioning in schizophrenia. Raloxifene, being a catechol-estrogen agonist, may have its effects modulated by COMT activity.
Answer
The study found that the COMT rs4818 CG genotype was associated with a significant beneficial effect of raloxifene on positive symptom severity, while the CC genotype was not. Additionally, a sex-specific analysis showed that the COMT rs737865 CT genotype was associated with a beneficial effect of raloxifene on total symptoms in men, and the TT genotype was associated with a beneficial effect on negative symptoms in women. This indicates that genetic variants in the COMT gene may influence the therapeutic effects of raloxifene in SSD, with potential sex-specific differences.
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