More than an “inverted-U”? An exploratory study of the association between the catechol-o-methyltransferase gene polymorphism and executive functions in Parkinson’s disease

Yi Jia Fang, Chun Hsiang Tan, Shao Ching Tu, Chien Yu Liu, Rwei-Ling Yu

Research output: Contribution to journalArticle

Abstract

Executive dysfunction is common in Parkinson’s disease (PD) patients. The catechol-O-met hyltransferase (COMT) Val158Met polymorphism has been proposed to affect executive functions (EFs) in the prefrontal cortex. The present study attempted to explore the influence of the COMT polymorphism on EFs in patients with PD. Fifty-four PD patients were recruited and underwent neuropsychological assessments for three core EFs. The COMT polymorphism was genotyped using the TaqMan SNP Genotyping Assay. Participants were divided into three study groups: Val homozygotes, heterozygotes, and Met homozygotes. The three COMT genotype groups had significantly different performances in set-shifting [χ 2 (2, 54) = 9.717, p = 0.008] and working memory tasks [χ 2 (2, 54) = 7.806, p = 0.020]. Post-hoc analyses revealed that PD Val homozygotes performed significantly poorer in the set-shifting task than did either the PD Met homozygotes (z = -2.628, p = 0.009) or PD heterozygotes (z = -2.212, p = 0.027). Our explorative results suggest that the putative level of prefrontal dopamine influenced set-shifting through a “cane-shaped” dopamine level-response relationship. Our results have clinical implications, which may influence PD treatment with dopamine in the future because the optimal dopamine level to maximize EFs may vary based on the clinical course and COMT polymorphism status. Further study recruiting a larger number of participants is needed to confirm our preliminary findings.

Original languageEnglish
Article numbere0214146
JournalPloS one
Volume14
Issue number3
DOIs
Publication statusPublished - 2019 Mar 1

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Catechol O-Methyltransferase
catechol
Parkinson disease
Executive Function
methyltransferases
Methyltransferases
Polymorphism
Parkinson Disease
Genes
Association reactions
genetic polymorphism
Homozygote
homozygosity
dopamine
Dopamine
genes
Heterozygote
heterozygosity
Canes
canes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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title = "More than an “inverted-U”? An exploratory study of the association between the catechol-o-methyltransferase gene polymorphism and executive functions in Parkinson’s disease",
abstract = "Executive dysfunction is common in Parkinson’s disease (PD) patients. The catechol-O-met hyltransferase (COMT) Val158Met polymorphism has been proposed to affect executive functions (EFs) in the prefrontal cortex. The present study attempted to explore the influence of the COMT polymorphism on EFs in patients with PD. Fifty-four PD patients were recruited and underwent neuropsychological assessments for three core EFs. The COMT polymorphism was genotyped using the TaqMan SNP Genotyping Assay. Participants were divided into three study groups: Val homozygotes, heterozygotes, and Met homozygotes. The three COMT genotype groups had significantly different performances in set-shifting [χ 2 (2, 54) = 9.717, p = 0.008] and working memory tasks [χ 2 (2, 54) = 7.806, p = 0.020]. Post-hoc analyses revealed that PD Val homozygotes performed significantly poorer in the set-shifting task than did either the PD Met homozygotes (z = -2.628, p = 0.009) or PD heterozygotes (z = -2.212, p = 0.027). Our explorative results suggest that the putative level of prefrontal dopamine influenced set-shifting through a “cane-shaped” dopamine level-response relationship. Our results have clinical implications, which may influence PD treatment with dopamine in the future because the optimal dopamine level to maximize EFs may vary based on the clinical course and COMT polymorphism status. Further study recruiting a larger number of participants is needed to confirm our preliminary findings.",
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More than an “inverted-U”? An exploratory study of the association between the catechol-o-methyltransferase gene polymorphism and executive functions in Parkinson’s disease. / Fang, Yi Jia; Tan, Chun Hsiang; Tu, Shao Ching; Liu, Chien Yu; Yu, Rwei-Ling.

In: PloS one, Vol. 14, No. 3, e0214146, 01.03.2019.

Research output: Contribution to journalArticle

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