The relationship between COMT genotype and the clinical effectiveness of tolcapone, a COMT inhibitor, in patients with Parkinson's disease.
Identifieur interne : 005588 ( Main/Exploration ); précédent : 005587; suivant : 005589The relationship between COMT genotype and the clinical effectiveness of tolcapone, a COMT inhibitor, in patients with Parkinson's disease.
Auteurs : D J Chong [Canada] ; O. Suchowersky ; C. Szumlanski ; R M Weinshilboum ; R. Brant ; N R CampbellSource :
- Clinical neuropharmacology [ 0362-5664 ]
English descriptors
- KwdEn :
- Aged, Antiparkinson Agents (blood), Antiparkinson Agents (therapeutic use), Benzophenones (adverse effects), Benzophenones (blood), Benzophenones (therapeutic use), Catechol O-Methyltransferase (genetics), Catechol O-Methyltransferase Inhibitors, Diarrhea (chemically induced), Diarrhea (enzymology), Diarrhea (genetics), Enzyme Inhibitors (adverse effects), Enzyme Inhibitors (blood), Enzyme Inhibitors (therapeutic use), Female, Genotype, Humans, Levodopa (administration & dosage), Levodopa (therapeutic use), Male, Middle Aged, Nitrophenols, Parkinson Disease (drug therapy), Parkinson Disease (genetics).
- MESH :
- chemical , administration & dosage : Levodopa.
- chemical , adverse effects : Benzophenones, Enzyme Inhibitors.
- chemical , blood : Antiparkinson Agents, Benzophenones, Enzyme Inhibitors.
- chemical , genetics : Catechol O-Methyltransferase.
- chemical , therapeutic use : Antiparkinson Agents, Benzophenones, Enzyme Inhibitors, Levodopa.
- chemically induced : Diarrhea.
- drug therapy : Parkinson Disease.
- enzymology : Diarrhea.
- genetics : Diarrhea, Parkinson Disease.
- Aged, Catechol O-Methyltransferase Inhibitors, Female, Genotype, Humans, Male, Middle Aged, Nitrophenols.
Abstract
Patients with Parkinson's Disease (PD) have a variable response to tolcapone, a catechol-O-methyltransferase (COMT) inhibitor. In addition, a subset of patients develop severe diarrhea as a side effect. Two codominant alleles for the COMT gene exist, coding for low and high activity, resulting in low-, medium-, and high-activity genotypes. This study investigates the relationship between this variation in genotype and clinical effects in patients with PD taking tolcapone. To investigate the relationship between COMT polymorphism and clinical response, 24 patients who completed tolcapone clinical trials provided blood samples for COMT genotype analysis. Change in levodopa dose and United Parkinson Disease Rating Scale (UPDRS) Part III (motor subscale) were analyzed at baseline, at 1-2 weeks, and 6 months after initiation of tolcapone. Genotype analysis was performed on seven patients who had diarrhea as a side effect. There was no significant correlation between genotype and improvement in UPDRS score (p = 0.29) according to a linear models approach that adjusted for the subject's severity of PD, tolcapone dose (either 100 or 200 mg three times daily) and initial differences in baseline scores. No significant difference was seen in change in daily levodopa intake and genotype. There was also no relation between diarrhea and COMT genotype. These results indicate that, in the treatment of Parkinson's disease, COMT genotype is not a major contributor to the clinical response to tolcapone.
PubMed: 10895397
Affiliations:
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Suchowersky</name></author><author><name sortKey="Szumlanski, C" sort="Szumlanski, C" uniqKey="Szumlanski C" first="C" last="Szumlanski">C. Szumlanski</name></author><author><name sortKey="Weinshilboum, R M" sort="Weinshilboum, R M" uniqKey="Weinshilboum R" first="R M" last="Weinshilboum">R M Weinshilboum</name></author><author><name sortKey="Brant, R" sort="Brant, R" uniqKey="Brant R" first="R" last="Brant">R. 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Suchowersky</name></author><author><name sortKey="Szumlanski, C" sort="Szumlanski, C" uniqKey="Szumlanski C" first="C" last="Szumlanski">C. Szumlanski</name></author><author><name sortKey="Weinshilboum, R M" sort="Weinshilboum, R M" uniqKey="Weinshilboum R" first="R M" last="Weinshilboum">R M Weinshilboum</name></author><author><name sortKey="Brant, R" sort="Brant, R" uniqKey="Brant R" first="R" last="Brant">R. Brant</name></author><author><name sortKey="Campbell, N R" sort="Campbell, N R" uniqKey="Campbell N" first="N R" last="Campbell">N R Campbell</name></author></analytic><series><title level="j">Clinical neuropharmacology</title><idno type="ISSN">0362-5664</idno></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Antiparkinson Agents (blood)</term><term>Antiparkinson Agents (therapeutic use)</term><term>Benzophenones (adverse effects)</term><term>Benzophenones (blood)</term><term>Benzophenones (therapeutic use)</term><term>Catechol O-Methyltransferase (genetics)</term><term>Catechol O-Methyltransferase Inhibitors</term><term>Diarrhea (chemically induced)</term><term>Diarrhea (enzymology)</term><term>Diarrhea (genetics)</term><term>Enzyme Inhibitors (adverse effects)</term><term>Enzyme Inhibitors (blood)</term><term>Enzyme Inhibitors (therapeutic use)</term><term>Female</term><term>Genotype</term><term>Humans</term><term>Levodopa (administration & dosage)</term><term>Levodopa (therapeutic use)</term><term>Male</term><term>Middle Aged</term><term>Nitrophenols</term><term>Parkinson Disease (drug therapy)</term><term>Parkinson Disease (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Benzophenones</term><term>Enzyme Inhibitors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antiparkinson Agents</term><term>Benzophenones</term><term>Enzyme Inhibitors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Catechol O-Methyltransferase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term><term>Benzophenones</term><term>Enzyme Inhibitors</term><term>Levodopa</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Diarrhea</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Diarrhea</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Diarrhea</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Catechol O-Methyltransferase Inhibitors</term><term>Female</term><term>Genotype</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Nitrophenols</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Patients with Parkinson's Disease (PD) have a variable response to tolcapone, a catechol-O-methyltransferase (COMT) inhibitor. In addition, a subset of patients develop severe diarrhea as a side effect. Two codominant alleles for the COMT gene exist, coding for low and high activity, resulting in low-, medium-, and high-activity genotypes. This study investigates the relationship between this variation in genotype and clinical effects in patients with PD taking tolcapone. To investigate the relationship between COMT polymorphism and clinical response, 24 patients who completed tolcapone clinical trials provided blood samples for COMT genotype analysis. Change in levodopa dose and United Parkinson Disease Rating Scale (UPDRS) Part III (motor subscale) were analyzed at baseline, at 1-2 weeks, and 6 months after initiation of tolcapone. Genotype analysis was performed on seven patients who had diarrhea as a side effect. There was no significant correlation between genotype and improvement in UPDRS score (p = 0.29) according to a linear models approach that adjusted for the subject's severity of PD, tolcapone dose (either 100 or 200 mg three times daily) and initial differences in baseline scores. No significant difference was seen in change in daily levodopa intake and genotype. There was also no relation between diarrhea and COMT genotype. These results indicate that, in the treatment of Parkinson's disease, COMT genotype is not a major contributor to the clinical response to tolcapone.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Alberta</li></region><settlement><li>Calgary</li></settlement><orgName><li>Université de Calgary</li></orgName></list><tree><noCountry><name sortKey="Brant, R" sort="Brant, R" uniqKey="Brant R" first="R" last="Brant">R. Brant</name><name sortKey="Campbell, N R" sort="Campbell, N R" uniqKey="Campbell N" first="N R" last="Campbell">N R Campbell</name><name sortKey="Suchowersky, O" sort="Suchowersky, O" uniqKey="Suchowersky O" first="O" last="Suchowersky">O. Suchowersky</name><name sortKey="Szumlanski, C" sort="Szumlanski, C" uniqKey="Szumlanski C" first="C" last="Szumlanski">C. Szumlanski</name><name sortKey="Weinshilboum, R M" sort="Weinshilboum, R M" uniqKey="Weinshilboum R" first="R M" last="Weinshilboum">R M Weinshilboum</name></noCountry><country name="Canada"><region name="Alberta"><name sortKey="Chong, D J" sort="Chong, D J" uniqKey="Chong D" first="D J" last="Chong">D J Chong</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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