title: Catechol-O-methyltransferase Val158Met polymorphism influences prefrontal executive function in early Parkinson's disease.
abstract: OBJECTIVE
  The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been proposed to be associated with increased risk of Parkinson's disease (PD) and have a specific impact on dopamine-mediated prefrontal executive function in an inverted-U curve manner. We explored the influence of this genetic polymorphism on prefrontal executive function in a well-established Chinese cohort of early PD patients with no current or past history of motor fluctuations or dyskinesias.
  
  
  METHODS
  Cognitive functions were assessed in 250 patients with early PD using Wechsler Adult Intelligence Scale-Chinese Revision (WAIS-RC) and Wechsler Memory Scale-Chinese Revision (WMS-RC). These patients and 300 healthy controls were subsequently genotyped for the COMT gene Val158Met polymorphism. We employed analysis of covariance (ANCOVA) and a stratified analysis to determine the associations between the COMT Val158Met genotype and cognitive functions.
  
  
  RESULTS
  The COMT Val158Met allele frequency and genotype distributions showed no statistically significant differences between PD patients and controls. However, patients with met/met genotype performed significantly worse on WAIS-RC similarities, a measure of executive function, compared to individuals with val/val genotype. Subsequent ANCOVA analysis revealed that COMT genotype interacted with sex and daily levodopa equivalent dose (LED) to influence executive function. Further stratified analysis showed that the lower-activity COMT met/met genotype has a detrimental effect on executive function among women.
  
  
  CONCLUSIONS
  Our results demonstrate that COMT Val158Met polymorphism is probably not associated with increased risk of PD, but has an effect on prefrontal executive function interacting with gender and dopaminergic medication.
authors.affiliation: Department of Neurology, Guangdong Neuroscience Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong Province 510080, PR China.
authors.forename: Youwen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Guangdong Neuroscience Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong Province 510080, PR China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Feng
authors.affiliation: Department of Neurology, Guangdong Neuroscience Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong Province 510080, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Nie
authors.affiliation: Department of Neurology, Guangdong Neuroscience Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong Province 510080, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Guangdong Neuroscience Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong Province 510080, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Gan
authors.affiliation: Department of Neurology, Guangdong Neuroscience Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong Province 510080, PR China.
authors.forename: Limin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, Guangdong Neuroscience Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong Province 510080, PR China.
authors.forename: Jiehao
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Guangdong Neuroscience Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong Province 510080, PR China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Neurology, Guangdong Neuroscience Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong Province 510080, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Neurology, Guangdong Neuroscience Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong Province 510080, PR China.
authors.forename: Ruiming
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Guangdong Neuroscience Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong Province 510080, PR China. Electronic address: wljgd68@163.com.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, Guangdong Neuroscience Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong Province 510080, PR China. Electronic address: yhzhangsd@126.com.
authors.forename: Yuhu
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics*; D056344:Executive Function / Q000502:physiology*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications* / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012720:Severity of Illness Index; D014633:Valine / Q000235:genetics; D014888:Wechsler Scales; D055815:Young Adult
chemical_list: D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine
keywords: COMT; Executive function; Parkinson's disease; Polymorphism; Prefrontal cortex