No association of a set of candidate genes on haloperidol side effects
We previously investigated a sample of patients during an active phase of psychosis in the search for genetic predictors of haloperidol induced side effects. In the present work we extend the genetic association analysis to a wider panel of genetic variations, including 508 variations located in 96...
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| description | We previously investigated a sample of patients during an active phase of psychosis in the search for genetic predictors of haloperidol induced side effects. In the present work we extend the genetic association analysis to a wider panel of genetic variations, including 508 variations located in 96 genes. The original sample included 96 patients. An independent group of 357 patients from the CATIE study served as a replication sample. Outcomes in the investigation sample were the variation through time of: 1) the ESRS and UKU total scores 2) ESRS and UKU subscales (neurologic and psychic were included) related to tremors and 3) ESRS and UKU subscales that do not relate to tremors. Outcome in the replication sample was the presence vs absence of motoric side effects from baseline to visit 1 (~ one month of treatment) as assessed by the AIMS scale test. Rs2242480 located in the CYP3A4 was associated with a different distribution of the UKU neurologic scores through time (permutated p = 0.047) along with a trend for a different haloperidol plasma levels (lower in CC subjects). This finding was not replicated in the CATIE sample. In conclusion, we did not find conclusive evidence for a major association between the investigated variations and haloperidol induced motoric side effects. |
| doi_str_mv | 10.1371/journal.pone.0044853 |
| format | Article |
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In the present work we extend the genetic association analysis to a wider panel of genetic variations, including 508 variations located in 96 genes. The original sample included 96 patients. An independent group of 357 patients from the CATIE study served as a replication sample. Outcomes in the investigation sample were the variation through time of: 1) the ESRS and UKU total scores 2) ESRS and UKU subscales (neurologic and psychic were included) related to tremors and 3) ESRS and UKU subscales that do not relate to tremors. Outcome in the replication sample was the presence vs absence of motoric side effects from baseline to visit 1 (~ one month of treatment) as assessed by the AIMS scale test. Rs2242480 located in the CYP3A4 was associated with a different distribution of the UKU neurologic scores through time (permutated p = 0.047) along with a trend for a different haloperidol plasma levels (lower in CC subjects). This finding was not replicated in the CATIE sample. In conclusion, we did not find conclusive evidence for a major association between the investigated variations and haloperidol induced motoric side effects.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0044853</identifier><identifier>PMID: 23077486</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Analysis of Variance ; Antipsychotic Agents - adverse effects ; Antipsychotic Agents - therapeutic use ; Antipsychotics ; Association analysis ; Biology ; Cardiovascular disease ; Central nervous system depressants ; Cytochrome ; Cytochrome P-450 ; Cytochrome P-450 CYP3A - genetics ; Cytochrome P-450 CYP3A - metabolism ; Dopamine ; Dosage and administration ; Drug therapy ; Enzymes ; Genes ; Genetic diversity ; Genomes ; Haloperidol ; Haloperidol - adverse effects ; Haloperidol - therapeutic use ; Health aspects ; Humans ; Medicine ; Mental disorders ; Metabolism ; Metabolites ; Patients ; Plasma levels ; Population ; Proteins ; Psychiatry ; Psychosis ; Psychotic Disorders - drug therapy ; Psychotic Disorders - genetics ; Psychotropic drugs ; Replication ; Schizophrenia ; Side effects ; Social and Behavioral Sciences ; Studies ; Tremors</subject><ispartof>PloS one, 2012-10, Vol.7 (10), p.e44853</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>Drago et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Drago et al 2012 Drago et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-39f036f2a699baf56d81f564906267f4fdc42aefa13d2addb159b3f4c5f32ed03</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471928/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471928/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23077486$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Drago, Antonio</creatorcontrib><creatorcontrib>Giegling, Ina</creatorcontrib><creatorcontrib>Schäfer, Martin</creatorcontrib><creatorcontrib>Hartmann, Annette M</creatorcontrib><creatorcontrib>Möller, Hans-Jürgen</creatorcontrib><creatorcontrib>De Ronchi, Diana</creatorcontrib><creatorcontrib>Stassen, Hans H</creatorcontrib><creatorcontrib>Serretti, Alessandro</creatorcontrib><creatorcontrib>Rujescu, Dan</creatorcontrib><title>No association of a set of candidate genes on haloperidol side effects</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>We previously investigated a sample of patients during an active phase of psychosis in the search for genetic predictors of haloperidol induced side effects. 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In conclusion, we did not find conclusive evidence for a major association between the investigated variations and haloperidol induced motoric side effects.</description><subject>Analysis</subject><subject>Analysis of Variance</subject><subject>Antipsychotic Agents - adverse effects</subject><subject>Antipsychotic Agents - therapeutic use</subject><subject>Antipsychotics</subject><subject>Association analysis</subject><subject>Biology</subject><subject>Cardiovascular disease</subject><subject>Central nervous system depressants</subject><subject>Cytochrome</subject><subject>Cytochrome P-450</subject><subject>Cytochrome P-450 CYP3A - genetics</subject><subject>Cytochrome P-450 CYP3A - metabolism</subject><subject>Dopamine</subject><subject>Dosage and administration</subject><subject>Drug therapy</subject><subject>Enzymes</subject><subject>Genes</subject><subject>Genetic diversity</subject><subject>Genomes</subject><subject>Haloperidol</subject><subject>Haloperidol - adverse effects</subject><subject>Haloperidol - 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| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Analysis Analysis of Variance Antipsychotic Agents - adverse effects Antipsychotic Agents - therapeutic use Antipsychotics Association analysis Biology Cardiovascular disease Central nervous system depressants Cytochrome Cytochrome P-450 Cytochrome P-450 CYP3A - genetics Cytochrome P-450 CYP3A - metabolism Dopamine Dosage and administration Drug therapy Enzymes Genes Genetic diversity Genomes Haloperidol Haloperidol - adverse effects Haloperidol - therapeutic use Health aspects Humans Medicine Mental disorders Metabolism Metabolites Patients Plasma levels Population Proteins Psychiatry Psychosis Psychotic Disorders - drug therapy Psychotic Disorders - genetics Psychotropic drugs Replication Schizophrenia Side effects Social and Behavioral Sciences Studies Tremors |
| title | No association of a set of candidate genes on haloperidol side effects |
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