Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
BMC Neurol. 2011 Jul 25;11:89. doi: 10.1186/1471-2377-11-89.
Parkinson's disease (PD) is characterized by alterations in dopaminergic neurotransmission. Genetic polymorphisms involved in dopaminergic neurotransmission may influence susceptibility to PD.
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.
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.
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.
帕金森病（PD）的特征是多巴胺能神经传递的改变。参与多巴胺能神经传递的遗传多态性可能影响 PD 的易感性。
我们研究了儿茶酚-O-甲基转移酶（COMT）、单胺氧化酶 B（MAOB）、多巴胺受体（DR）D2 和 DRD4 多态性与 PD 风险的关系，并特别关注日本人群中 238 例 PD 患者和 369 例对照者中与吸烟的相互作用。
与 AG 和 GG 基因型组合相比，MAOB rs1799836 的 AA 基因型的个体患 PD 的风险显著增加（比值比（OR）=1.70，95%置信区间（CI）=1.12-2.58）。与 GG 基因型相比，COMT rs4680 的 AA 基因型与 PD 风险略有增加（OR=1.86，95%CI=0.98-3.50）。DRD2 rs1800497 和 DRD4 rs1800955 多态性与 PD 无关。提示 COMT-吸烟相互作用，rs4680 的 GA 和 AA 基因型与非吸烟相结合可显著增加风险（OR=3.97，95%CI=2.13-7.41），高于 AA 基因型和吸烟史（P 交互=0.061）。未观察到吸烟与其他多态性之间的相互作用。
COMT rs4680 和 MAOB rs1799836 多态性可能会增加日本人群患 PD 风险。未来涉及更大的对照和病例人群以及更好的农药暴露史的研究无疑将导致更深入地了解多巴胺通路中涉及的多态性在 PD 中的作用。
