Functional COMT variant predicts response to high dose pyridoxine in Parkinson's disease
Identifieur interne : 000490 ( Istex/Corpus ); précédent : 000489; suivant : 000491Functional COMT variant predicts response to high dose pyridoxine in Parkinson's disease
Auteurs : Eng Tan ; Sin Cheah ; Stephanie Fook ; Kenneth Yew ; V Chandran ; Sau Lum ; Zhao YiSource :
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics [ 1552-4841 ] ; 2005-08-05.
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- KwdEn :
Abstract
Pyridoxal‐5‐phosphate, the biological active form of pyridoxine, is a cofactor for dopa‐decarboxylase (DDC) enzyme. Pyridoxine may augment the conversion of levodopa to dopamine in the periphery and therefore decrease availability of levodopa to the brain. However, this effect can be negated in the presence of a DDC inhibitor, which potentiates plasma levodopa level. A single nucleotide polymorphism at the nucleotide 1947 in the catechol‐O‐methyltransferase (COMT) gene encodes the high (COMTH) and low activity (COMTL) forms of the enzyme. In this study, we examined the effect of the COMTL allele on the clinical response to pyridoxine in Parkinson's disease (PD) patients. PD patients who were on stable and optimized dose of levodopa were included in this study. Their mean motor and activities of living score improved after high dose pyridoxine (P = 0.09, P = 0.04), and worsened after a washout period (P = 0.005, P = 0.001). Using a multivariate model, the presence of the COMTL allele predicted response to pyridoxine, with the best outcome observed in COMTL/L homozygotes. Our observational study suggests that the status the functional COMTL variant may be potentially useful to select PD patients for high dose pyridoxine therapy. © 2005 Wiley‐Liss, Inc.
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DOI: 10.1002/ajmg.b.30198
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<front><div type="abstract" xml:lang="en">Pyridoxal‐5‐phosphate, the biological active form of pyridoxine, is a cofactor for dopa‐decarboxylase (DDC) enzyme. Pyridoxine may augment the conversion of levodopa to dopamine in the periphery and therefore decrease availability of levodopa to the brain. However, this effect can be negated in the presence of a DDC inhibitor, which potentiates plasma levodopa level. A single nucleotide polymorphism at the nucleotide 1947 in the catechol‐O‐methyltransferase (COMT) gene encodes the high (COMTH) and low activity (COMTL) forms of the enzyme. In this study, we examined the effect of the COMTL allele on the clinical response to pyridoxine in Parkinson's disease (PD) patients. PD patients who were on stable and optimized dose of levodopa were included in this study. Their mean motor and activities of living score improved after high dose pyridoxine (P = 0.09, P = 0.04), and worsened after a washout period (P = 0.005, P = 0.001). Using a multivariate model, the presence of the COMTL allele predicted response to pyridoxine, with the best outcome observed in COMTL/L homozygotes. Our observational study suggests that the status the functional COMTL variant may be potentially useful to select PD patients for high dose pyridoxine therapy. © 2005 Wiley‐Liss, Inc.</div>
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</personName>
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<creator xml:id="au6" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Sau‐Ying</givenNames>
<familyName>Lum</familyName>
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<creator xml:id="au7" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Zhao</givenNames>
<familyName>Yi</familyName>
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<affiliationGroup><affiliation xml:id="af1" countryCode="SG" type="organization"><unparsedAffiliation>Department of Neurology, Singapore General Hospital, Singapore</unparsedAffiliation>
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<affiliation xml:id="af2" countryCode="SG" type="organization"><unparsedAffiliation>Department of Pharmacy, Singapore General Hospital, Singapore</unparsedAffiliation>
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<affiliation xml:id="af3" countryCode="SG" type="organization"><unparsedAffiliation>Department of Clinical Research, Singapore General Hospital, Singapore</unparsedAffiliation>
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<affiliation xml:id="af4" countryCode="SG" type="organization"><unparsedAffiliation>National Neuroscience Institute, Singapore General Hospital, Singapore</unparsedAffiliation>
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<keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">Parkinson's disease</keyword>
<keyword xml:id="kwd2">pyridoxine</keyword>
<keyword xml:id="kwd3">COMT variant</keyword>
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<fundingInfo><fundingAgency>National Medical Research Council</fundingAgency>
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<abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title>
<p>Pyridoxal‐5‐phosphate, the biological active form of pyridoxine, is a cofactor for dopa‐decarboxylase (DDC) enzyme. Pyridoxine may augment the conversion of levodopa to dopamine in the periphery and therefore decrease availability of levodopa to the brain. However, this effect can be negated in the presence of a DDC inhibitor, which potentiates plasma levodopa level. A single nucleotide polymorphism at the nucleotide 1947 in the catechol‐<i>O</i>
‐methyltransferase (<i>COMT</i>
) gene encodes the high (COMT<sup>H</sup>
) and low activity (COMT<sup>L</sup>
) forms of the enzyme. In this study, we examined the effect of the COMT<sup>L</sup>
allele on the clinical response to pyridoxine in Parkinson's disease (PD) patients. PD patients who were on stable and optimized dose of levodopa were included in this study. Their mean motor and activities of living score improved after high dose pyridoxine (<i>P</i>
= 0.09, <i>P</i>
= 0.04), and worsened after a washout period (<i>P</i>
= 0.005, <i>P</i>
= 0.001). Using a multivariate model, the presence of the COMT<sup>L</sup>
allele predicted response to pyridoxine, with the best outcome observed in COMT<sup>L/L</sup>
homozygotes. Our observational study suggests that the status the functional COMT<sup>L</sup>
variant may be potentially useful to select PD patients for high dose pyridoxine therapy. © 2005 Wiley‐Liss, Inc.</p>
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<mods version="3.6"><titleInfo lang="en"><title>Functional COMT variant predicts response to high dose pyridoxine in Parkinson's disease</title>
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<titleInfo type="alternative" contentType="CDATA" lang="en"><title>Functional COMT variant predicts response to high dose pyridoxine in Parkinson's disease</title>
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<name type="personal"><namePart type="given">Eng‐King</namePart>
<namePart type="family">Tan</namePart>
<affiliation>Department of Neurology, Singapore General Hospital, Singapore</affiliation>
<affiliation>National Neuroscience Institute, Singapore General Hospital, Singapore</affiliation>
<affiliation>SingHealth Research, Singapore General Hospital, Singapore</affiliation>
<description>Correspondence: Department of Neurology, Singapore General Hospital, Outram Road, Singapore 169608.</description>
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<name type="personal"><namePart type="given">Sin‐Yun</namePart>
<namePart type="family">Cheah</namePart>
<affiliation>Department of Neurology, Singapore General Hospital, Singapore</affiliation>
<affiliation>Department of Pharmacy, Singapore General Hospital, Singapore</affiliation>
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</role>
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<name type="personal"><namePart type="given">Stephanie</namePart>
<namePart type="family">Fook‐Chong</namePart>
<affiliation>Department of Clinical Research, Singapore General Hospital, Singapore</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
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<name type="personal"><namePart type="given">Kenneth</namePart>
<namePart type="family">Yew</namePart>
<affiliation>Department of Neurology, Singapore General Hospital, Singapore</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
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<name type="personal"><namePart type="given">V.R.</namePart>
<namePart type="family">Chandran</namePart>
<affiliation>Department of Clinical Research, Singapore General Hospital, Singapore</affiliation>
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<name type="personal"><namePart type="given">Sau‐Ying</namePart>
<namePart type="family">Lum</namePart>
<affiliation>Department of Neurology, Singapore General Hospital, Singapore</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
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<name type="personal"><namePart type="given">Zhao</namePart>
<namePart type="family">Yi</namePart>
<affiliation>Department of Clinical Research, Singapore General Hospital, Singapore</affiliation>
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<dateIssued encoding="w3cdtf">2005-08-05</dateIssued>
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<abstract lang="en">Pyridoxal‐5‐phosphate, the biological active form of pyridoxine, is a cofactor for dopa‐decarboxylase (DDC) enzyme. Pyridoxine may augment the conversion of levodopa to dopamine in the periphery and therefore decrease availability of levodopa to the brain. However, this effect can be negated in the presence of a DDC inhibitor, which potentiates plasma levodopa level. A single nucleotide polymorphism at the nucleotide 1947 in the catechol‐O‐methyltransferase (COMT) gene encodes the high (COMTH) and low activity (COMTL) forms of the enzyme. In this study, we examined the effect of the COMTL allele on the clinical response to pyridoxine in Parkinson's disease (PD) patients. PD patients who were on stable and optimized dose of levodopa were included in this study. Their mean motor and activities of living score improved after high dose pyridoxine (P = 0.09, P = 0.04), and worsened after a washout period (P = 0.005, P = 0.001). Using a multivariate model, the presence of the COMTL allele predicted response to pyridoxine, with the best outcome observed in COMTL/L homozygotes. Our observational study suggests that the status the functional COMTL variant may be potentially useful to select PD patients for high dose pyridoxine therapy. © 2005 Wiley‐Liss, Inc.</abstract>
<note type="funding">National Medical Research Council</note>
<subject lang="en"><genre>Keywords</genre>
<topic>Parkinson's disease</topic>
<topic>pyridoxine</topic>
<topic>COMT variant</topic>
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<relatedItem type="host"><titleInfo><title>American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title>
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<titleInfo type="abbreviated"><title>Am. J. Med. Genet.</title>
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<identifier type="ISSN">1552-4841</identifier>
<identifier type="eISSN">1552-485X</identifier>
<identifier type="DOI">10.1002/(ISSN)1552-485X</identifier>
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<part><date>2005</date>
<detail type="volume"><caption>vol.</caption>
<number>137B</number>
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<end>4</end>
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<relatedItem type="preceding"><titleInfo><title>American Journal of Medical Genetics</title>
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<identifier type="ISSN">0148-7299</identifier>
<identifier type="ISSN">1096-8628</identifier>
<part><date point="end">2004</date>
</part>
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