title: Genetic polymorphisms involved in dopaminergic neurotransmission and risk for Parkinson's disease in a Japanese population.
abstract: BACKGROUND
  Parkinson's disease (PD) is characterized by alterations in dopaminergic neurotransmission. Genetic polymorphisms involved in dopaminergic neurotransmission may influence susceptibility to PD.
  
  
  METHODS
  We investigated the relationship of catechol-O-methyltransferase (COMT), monoamine oxidase B (MAOB), dopamine receptor (DR) D2 and DRD4 polymorphisms and PD risk with special attention to the interaction with cigarette smoking among 238 patients with PD and 369 controls in a Japanese population.
  
  
  RESULTS
  Subjects with the AA genotype of MAOB rs1799836 showed a significantly increased risk of PD (odds ratio (OR) = 1.70, 95% confidence interval (CI) = 1.12 - 2.58) compared with the AG and GG genotypes combined. The AA genotype of COMT rs4680 was marginally associated with an increased risk of PD (OR = 1.86, 95% CI = 0.98 - 3.50) compared with the GG genotype. The DRD2 rs1800497 and DRD4 rs1800955 polymorphisms showed no association with PD. A COMT -smoking interaction was suggested, with the combined GA and AA genotypes of rs4680 and non-smoking conferring significantly higher risk (OR = 3.97, 95% CI = 2.13 - 7.41) than the AA genotype and a history of smoking (P for interaction = 0.061). No interactions of smoking with other polymorphisms were observed.
  
  
  CONCLUSIONS
  The COMT rs4680 and MAOB rs1799836 polymorphisms may increase susceptibility to PD risk among Japanese. Future studies involving larger control and case populations and better pesticide exposure histories will undoubtedly lead to a more thorough understanding of the role of the polymorphisms involved in the dopamine pathway in PD.
authors.affiliation: Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. chikako@phealth.med.kyushu-u.ac.jp
authors.forename: Chikako
authors.initials: C
authors.lastname: Kiyohara
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Miyake
authors.forename: Midori
authors.initials: M
authors.lastname: Koyanagi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fujimoto
authors.forename: Senji
authors.initials: S
authors.lastname: Shirasawa
authors.forename: Keiko
authors.initials: K
authors.lastname: Tanaka
authors.forename: Wakaba
authors.initials: W
authors.lastname: Fukushima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sasaki
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tsuboi
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yamada
authors.forename: Tomoko
authors.initials: T
authors.lastname: Oeda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimada
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Kawamura
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Sakae
authors.forename: Hidenao
authors.initials: H
authors.lastname: Fukuyama
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hirota
authors.forename: Masaki
authors.initials: M
authors.lastname: Nagai
mesh_terms: D044466:Asian People / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking
chemical_list: C493599:DRD4 protein, human; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase