APOE and CYP2E1 polymorphisms, alcohol consumption, and Parkinson's disease in a Japanese population

Chikako Kiyohara, Yoshihiro Miyake, Midori Koyanagi, Takahiro Fujimoto, Senji Shirasawa, Keiko Tanaka, Wakaba Fukushima, Satoshi Sasaki, Yoshio Tsuboi, Tatsuo Yamada, Tomoko Oeda, Takami Miki, Nobutoshi Kawamura, Nobutaka Sakae, Hidenao Fukuyama, Yoshio Hirota, Masaki Nagai

Research output: Contribution to journalArticle

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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 ε2, ε3, and ε4 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.

Original languageEnglish
Pages (from-to)1335-1344
Number of pages10
JournalJournal of Neural Transmission
Volume118
Issue number9
DOIs
Publication statusPublished - Sep 1 2011

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Cytochrome P-450 CYP2E1
Apolipoproteins E
Alcohol Drinking
Parkinson Disease
Population
Reactive Oxygen Species
Oxidative Stress
Alleles
Genotype
Apolipoprotein E3
Apolipoprotein E4
Disease Susceptibility
Neurotoxins
Neurodegenerative Diseases
Genes
Odds Ratio
Alcohols
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

APOE and CYP2E1 polymorphisms, alcohol consumption, and Parkinson's disease in a Japanese population. / Kiyohara, Chikako; Miyake, Yoshihiro; Koyanagi, Midori; Fujimoto, Takahiro; Shirasawa, Senji; Tanaka, Keiko; Fukushima, Wakaba; Sasaki, Satoshi; Tsuboi, Yoshio; Yamada, Tatsuo; Oeda, Tomoko; Miki, Takami; Kawamura, Nobutoshi; Sakae, Nobutaka; Fukuyama, Hidenao; Hirota, Yoshio; Nagai, Masaki.

In: Journal of Neural Transmission, Vol. 118, No. 9, 01.09.2011, p. 1335-1344.

Research output: Contribution to journalArticle

Kiyohara, C, Miyake, Y, Koyanagi, M, Fujimoto, T, Shirasawa, S, Tanaka, K, Fukushima, W, Sasaki, S, Tsuboi, Y, Yamada, T, Oeda, T, Miki, T, Kawamura, N, Sakae, N, Fukuyama, H, Hirota, Y & Nagai, M 2011, 'APOE and CYP2E1 polymorphisms, alcohol consumption, and Parkinson's disease in a Japanese population', Journal of Neural Transmission, vol. 118, no. 9, pp. 1335-1344. https://doi.org/10.1007/s00702-011-0612-y
Kiyohara, Chikako ; Miyake, Yoshihiro ; Koyanagi, Midori ; Fujimoto, Takahiro ; Shirasawa, Senji ; Tanaka, Keiko ; Fukushima, Wakaba ; Sasaki, Satoshi ; Tsuboi, Yoshio ; Yamada, Tatsuo ; Oeda, Tomoko ; Miki, Takami ; Kawamura, Nobutoshi ; Sakae, Nobutaka ; Fukuyama, Hidenao ; Hirota, Yoshio ; Nagai, Masaki. / APOE and CYP2E1 polymorphisms, alcohol consumption, and Parkinson's disease in a Japanese population. In: Journal of Neural Transmission. 2011 ; Vol. 118, No. 9. pp. 1335-1344.
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AU - Shirasawa, Senji

AU - Tanaka, Keiko

AU - Fukushima, Wakaba

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AU - Tsuboi, Yoshio

AU - Yamada, Tatsuo

AU - Oeda, Tomoko

AU - Miki, Takami

AU - Kawamura, Nobutoshi

AU - Sakae, Nobutaka

AU - Fukuyama, Hidenao

AU - Hirota, Yoshio

AU - Nagai, Masaki

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N2 - 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 ε2, ε3, and ε4 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.

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