Meta-Analysis of the Effects of the Catechol-O-Methyltransferase Val158/108Met Polymorphism on Parkinson’s Disease Susceptibility and Cognitive Dysfunction.

Meta-Analysis of the Effects of the Catechol-O-Methyltransferase Val158/108Met Polymorphism on Parkinson’s Disease Susceptibility and Cognitive Dysfunction.

Publication date: Feb 14, 2019

Background: There is a continued debate and inconsistent findings in previous literature about the relationship of catechol-O-methyltransferase (COMT) and Parkinson’s disease (PD) susceptibility as well as cognitive dysfunction. To substantiate this existing gap, we comprehensively examine COMT genotype effects on the development of PD and test the hypothesis that the Met158 allele of the COMT gene is associated with cognitive dysfunction by conducting a meta-analysis review. Methods: PubMed/MEDLINE, Embase, Cochrane databases search (18/30/08) yielded 49 included studies. Data were extracted by two reviewers and included COMT genotype, publication year, diagnostic status, ancestry, the proportion of male participants, and whether genotype frequencies were consistent with Hardy-Weinberg equilibrium. Unadjusted odds ratios (ORs) were used to derive pooled estimates of PD risk overall and in subgroups defined by ethnicity, gender, and onset of disease. Moreover, the association of certain cognitive domains in PD and COMT gene type was explored. Meta-analyses were performed using random-effect models and p value-based methods. All statistical tests were two-sided. The present study was registered with PROSPERO (CRD42018087323). Results: In the current studies, we found no association between COMT Val158/108Met polymorphism and PD susceptibility. However, the gender-stratified analyses revealed marginally significant effects in heterozygote model analyses in women (P = 0.053). In addition, stratification according to onset of PD also shows significant effects of COMT Val158/108Met polymorphism on late-onset population both in recessive (P = 0.017) and allelic (P = 0.017) genetic models. For the intelligence quotient (IQ) score and Unified Parkinson Disease Rating Scale III (UPDRS III), there was no evidence for genetic association, except in subgroup analyses in Asian populations (IQ score, P = 0.016; UPDRS III, P

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Tang, C., Wang, W., Shi, M., Zhang, N., Zhou, X., Li, X., Ma, C., Chen, G., Xiang, J., and Gao, D. Meta-Analysis of the Effects of the Catechol-O-Methyltransferase Val158/108Met Polymorphism on Parkinson’s Disease Susceptibility and Cognitive Dysfunction. 22549. 2019 Front Genet (10):

Concepts Keywords
Allele Clinical medicine
Allelic Medicine
Asian Branches of biology
Catechol Catechol-O-methyltransferase
Cochrane COMT cognitive dysfunction
Cognitive Rs4680
Cognitive Dysfunction Genotype
COMT
Embase
Equilibrium
Gender
Genetic
Genetic Association
Genotype
Heterozygote
Intelligence Quotient IQ
IQ
MEDLINE
Meta Analysis
Methionine
Methyltransferase
Odds Ratios
Parkinson
Polymorphism
PROSPERO
PubMed
Recessive
Stratification
Subgroup
Valine

Semantics

Type Source Name
drug DRUGBANK L-Valine
drug DRUGBANK Methionine
disease DOID Parkinson Disease
disease MESH Parkinson Disease
disease MESH heterozygote
disease MESH development
gene UNIPROT RASA1
gene UNIPROT COMT
disease MESH Cognitive Dysfunction

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