Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Jul 25:11:89.
doi: 10.1186/1471-2377-11-89.

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

Chikako Kiyohara  1 , 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; Fukuoka Kinki Parkinson's Disease Study Group
Collaborators, Affiliations

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

Chikako Kiyohara et al. BMC Neurol. .

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.

PubMed Disclaimer

References

    1. Jaber M, Robinson SW, Missale C, Caron MG. Dopamine receptors and brain function. Neuropharmacology. 1996;35:1503–1519. - PubMed
    1. Hornykiewicz O. Dopamine (3-hydroxytyramine) and brain function. Pharmacol Rev. 1966;18:925–964. - PubMed
    1. Rubinstein M, Phillips TJ, Bunzow JR, Falzone TL, Dziewczapolski G, Zhang G, Fang Y, Larson JL, McDougall JA, Chester JA, Saez C, Pugsley TA, Gershanik O, Low MJ, Grandy DK. Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine. Cell. 1997;90:991–1001. doi: 10.1016/S0092-8674(00)80365-7. - DOI - PubMed
    1. Jellinger K, Kienzl E, Rumpelmair G, Riederer P, Stachelberger H, Ben-Shachar D, Youdim MB. Iron-melanin complex in substantia nigra of parkinsonian brains: an x-ray microanalysis. J Neurochem. 1992;59:1168–1171. doi: 10.1111/j.1471-4159.1992.tb08362.x. - DOI - PubMed
    1. Syvanen AC, Tilgmann C, Rinne J, Ulmanen I. Genetic polymorphism of catechol-O-methyltransferase (COMT): correlation of genotype with individual variation of S-COMT activity and comparison of the allele frequencies in the normal population and parkinsonian patients in Finland. Pharmacogenetics. 1997;7:65–71. doi: 10.1097/00008571-199702000-00009. - DOI - PubMed

Publication types