title: APOE and CYP2E1 polymorphisms, alcohol consumption, and Parkinson's disease in a Japanese population.
abstract: Apolipoprotein E (APOE) is associated with increased oxidative stress, which is caused by reactive oxygen species (ROS). Enhanced cytochrome P450 2E1 (CYP2E1) activity may also increase formation of neurotoxins such as ROS. As Parkinson's disease (PD) is a neurodegenerative disorder, both the APOE and CYP2E1 genes that are involved in neurodegeneration by oxidative stress may be associated with PD risk. We investigated the relationship of the APOE and CYP2E1 rs2864987 polymorphisms and PD risk with special attention to the interaction with alcohol consumption among 238 patients with PD and 296 controls in a Japanese population. The frequencies of the ɛ2, ɛ3, and ɛ4 alleles of the APOE polymorphism among controls were 3.72, 86.7, and 9.63%, respectively. As compared with the APOE ε3/ε3 genotype, the 2/ε4 genotype was associated with an increased risk of PD (adjusted odds ratio (OR) = 9.50, 95% (confidence interval) CI = 1.12-80.6). The presence of the ε3 allele was associated with a decreased risk of PD. Meanwhile, CYP2E1 rs2864987 was not associated with PD risk. Although CYP2E1 is involved in the metabolism of alcohol, there was no evidence of interaction between alcohol consumption and CYP2E1 rs2864987. Our results suggested that the APOE polymorphism might play an important role in PD susceptibility in our Japanese population. Future studies involving larger control and case populations and better alcohol consumption histories will undoubtedly lead to a more thorough understanding of the role of polymorphisms of genes related to the generation of ROS in PD development.
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: Takami
authors.initials: T
authors.lastname: Miki
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: D000368:Aged; D000428:Alcohol Drinking / Q000208:ethnology* / Q000235:genetics*; D053329:Apolipoprotein E2 / Q000235:genetics*; D053318:Apolipoprotein E3 / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000201:enzymology / Q000208:ethnology* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors
chemical_list: D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D019392:Cytochrome P-450 CYP2E1