Functional COMT variant predicts response to high dose pyridoxine in Parkinson's disease
Identifieur interne : 000D08 ( Istex/Checkpoint ); précédent : 000D07; suivant : 000D09Functional COMT variant predicts response to high dose pyridoxine in Parkinson's disease
Auteurs : Eng Tan [Singapour] ; Sin Cheah [Singapour] ; Stephanie Fook [Singapour] ; Kenneth Yew [Singapour] ; V Chandran [Singapour] ; Sau Lum [Singapour] ; Zhao Yi [Singapour]Source :
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics [ 1552-4841 ] ; 2005-08-05.
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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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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></front></TEI><affiliations><list><country><li>Singapour</li></country></list><tree><country name="Singapour"><noRegion><name sortKey="Tan, Eng Ing" sort="Tan, Eng Ing" uniqKey="Tan E" first="Eng" last="Tan">Eng Tan</name></noRegion><name sortKey="Chandran, V R" sort="Chandran, V R" uniqKey="Chandran V" first="V" last="Chandran">V Chandran</name><name sortKey="Cheah, Sin Un" sort="Cheah, Sin Un" uniqKey="Cheah S" first="Sin" last="Cheah">Sin Cheah</name><name sortKey="Cheah, Sin Un" sort="Cheah, Sin Un" uniqKey="Cheah S" first="Sin" last="Cheah">Sin Cheah</name><name sortKey="Fook Hong, Stephanie" sort="Fook Hong, Stephanie" uniqKey="Fook Hong S" first="Stephanie" last="Fook">Stephanie Fook</name><name sortKey="Lum, Sau Ing" sort="Lum, Sau Ing" uniqKey="Lum S" first="Sau" last="Lum">Sau Lum</name><name sortKey="Tan, Eng Ing" sort="Tan, Eng Ing" uniqKey="Tan E" first="Eng" last="Tan">Eng Tan</name><name sortKey="Tan, Eng Ing" sort="Tan, Eng Ing" uniqKey="Tan E" first="Eng" last="Tan">Eng Tan</name><name sortKey="Yew, Kenneth" sort="Yew, Kenneth" uniqKey="Yew K" first="Kenneth" last="Yew">Kenneth Yew</name><name sortKey="Yi, Zhao" sort="Yi, Zhao" uniqKey="Yi Z" first="Zhao" last="Yi">Zhao Yi</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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