Genetic polymorphisms involved in dopaminergic neurotransmission and risk for 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, Hiroyuki Shimada, Nobutoshi Kawamura, Nobutaka Sakae, Hidenao Fukuyama, Yoshio Hirota, Masaki Nagai

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number89
JournalBMC neurology
Volume11
DOIs
Publication statusPublished - Jul 25 2011

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Genetic Polymorphisms
Synaptic Transmission
Parkinson Disease
Catechol O-Methyltransferase
Genotype
Population
Monoamine Oxidase
Smoking
Odds Ratio
Confidence Intervals
Dopamine D2 Receptors
Pesticides
Dopamine

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

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Genetic polymorphisms involved in dopaminergic neurotransmission and risk for 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; Shimada, Hiroyuki; Kawamura, Nobutoshi; Sakae, Nobutaka; Fukuyama, Hidenao; Hirota, Yoshio; Nagai, Masaki.

In: BMC neurology, Vol. 11, 89, 25.07.2011.

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, Shimada, H, Kawamura, N, Sakae, N, Fukuyama, H, Hirota, Y & Nagai, M 2011, 'Genetic polymorphisms involved in dopaminergic neurotransmission and risk for Parkinson's disease in a Japanese population', BMC neurology, vol. 11, 89. https://doi.org/10.1186/1471-2377-11-89
Kiyohara, Chikako ; Miyake, Yoshihiro ; Koyanagi, Midori ; Fujimoto, Takahiro ; Shirasawa, Senji ; Tanaka, Keiko ; Fukushima, Wakaba ; Sasaki, Satoshi ; Tsuboi, Yoshio ; Yamada, Tatsuo ; Oeda, Tomoko ; Shimada, Hiroyuki ; Kawamura, Nobutoshi ; Sakae, Nobutaka ; Fukuyama, Hidenao ; Hirota, Yoshio ; Nagai, Masaki. / Genetic polymorphisms involved in dopaminergic neurotransmission and risk for Parkinson's disease in a Japanese population. In: BMC neurology. 2011 ; Vol. 11.
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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.",
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AU - Kiyohara, Chikako

AU - Miyake, Yoshihiro

AU - Koyanagi, Midori

AU - Fujimoto, Takahiro

AU - Shirasawa, Senji

AU - Tanaka, Keiko

AU - Fukushima, Wakaba

AU - Sasaki, Satoshi

AU - Tsuboi, Yoshio

AU - Yamada, Tatsuo

AU - Oeda, Tomoko

AU - Shimada, Hiroyuki

AU - Kawamura, Nobutoshi

AU - Sakae, Nobutaka

AU - Fukuyama, Hidenao

AU - Hirota, Yoshio

AU - Nagai, Masaki

PY - 2011/7/25

Y1 - 2011/7/25

N2 - 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.

AB - 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.

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