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Open Access Research article

Genetic polymorphisms involved in dopaminergic neurotransmission and risk for Parkinson's disease in a Japanese population

Chikako Kiyohara1*, Yoshihiro Miyake2, Midori Koyanagi3, Takahiro Fujimoto3, Senji Shirasawa3, Keiko Tanaka2, Wakaba Fukushima4, Satoshi Sasaki5, Yoshio Tsuboi6, Tatsuo Yamada6, Tomoko Oeda7, Hiroyuki Shimada8, Nobutoshi Kawamura9, Nobutaka Sakae9, Hidenao Fukuyama10, Yoshio Hirota4, Masaki Nagai11 and Fukuoka Kinki Parkinson's Disease Study Group12

Author Affiliations

1 Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

2 Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University, Fukuoka, Japan

3 Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan

4 Department of Public Health, Osaka City University Graduate School of Medicine, Osaka, Japan

5 Department of Social and Preventive Epidemiology, School of Public Health, The University of Tokyo, Tokyo, Japan

6 Department of Neurology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan

7 Clinical Research Institute and Department of Neurology, Utano National Hospital, Kyoto, Japan

8 Department of Geriatrics and Neurology, Osaka City University Graduate School of Medicine, Osaka, Japan

9 Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

10 Human Brain Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan

11 Department of Public Health, Saitama Medical University Faculty of Medicine, Saitama, Japan

12 Other members of the Study Group are listed in the Appendix

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BMC Neurology 2011, 11:89  doi:10.1186/1471-2377-11-89

Published: 25 July 2011

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.