The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry · 2010
The catechol-O-methyl-transferase gene in tardive dyskinesia.
СтатьяМетаанализПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Zai Clement C, Tiwari Arun K, Müller Daniel J, De Luca Vincenzo, Shinkai Takahiro, Shaikh Sajid, Ni Xingqun, Sibony David, Voineskos Aristotle N, Meltzer Herbert Y, Lieberman Jeffrey A, Potkin Steven G, Remington Gary, Kennedy James L
Аннотация
UNLABELLED: Tardive dyskinesia (TD) is a severe and potentially irreversible motor side effect linked to long-term antipsychotic exposure. Changes in dopamine neurotransmission have been implicated in the etiology of TD, and catechol-O-methyl-transferase (COMT) is an enzyme that metabolizes dopamine.
OBJECTIVES: We investigated five single-nucleotide polymorphisms in addition to the functional Val158Met variant spanning the COMT gene for association with TD.
METHODS: We analyzed the six COMT single-nucleotide polymorphisms in a sample of schizophrenia/schizoaffective disorder patients (n=226; 196 Caucasians and 30 African Americans).
RESULTS: We found a significant association between the marker rs165599 in the 3' untranslated region of COMT and TD (AA versus G-carrier: OR(AA)=2.22, 95% CI:1.23-4.03; P=0.007). The association appeared to be originating from males. We did not find a significant association of the other five tested polymorphisms with TD in our samples. We performed a sex-stratified meta-analysis across all of the published studies (n=6 plus our own data) of COMT and TD, and found an association between ValVal genotype and TD in females (OR(ValVal)=1.63, 95% CI: 1.09-2.45; P=0.019) but not in males.
CONCLUSIONS: Overall, our results suggest that the COMT gene may have a minor but consistent role in TD, although sex-stratified studies with additional markers in larger clinical samples should be performed.
OBJECTIVES: We investigated five single-nucleotide polymorphisms in addition to the functional Val158Met variant spanning the COMT gene for association with TD.
METHODS: We analyzed the six COMT single-nucleotide polymorphisms in a sample of schizophrenia/schizoaffective disorder patients (n=226; 196 Caucasians and 30 African Americans).
RESULTS: We found a significant association between the marker rs165599 in the 3' untranslated region of COMT and TD (AA versus G-carrier: OR(AA)=2.22, 95% CI:1.23-4.03; P=0.007). The association appeared to be originating from males. We did not find a significant association of the other five tested polymorphisms with TD in our samples. We performed a sex-stratified meta-analysis across all of the published studies (n=6 plus our own data) of COMT and TD, and found an association between ValVal genotype and TD in females (OR(ValVal)=1.63, 95% CI: 1.09-2.45; P=0.019) but not in males.
CONCLUSIONS: Overall, our results suggest that the COMT gene may have a minor but consistent role in TD, although sex-stratified studies with additional markers in larger clinical samples should be performed.