Costa-Mallen P, Costa L G, Smith-Weller T, Franklin G M, Swanson P D, Checkoway H
Department of Environmental Health, University of Washington School of Public Health and Community Medicine, 4225 Roosevelt Way NE 100, Seattle, WA 98105-6099, USA.
J Neurol Neurosurg Psychiatry. 2000 Oct;69(4):535-7. doi: 10.1136/jnnp.69.4.535.
Genetic polymorphisms of dopamine D2 receptors (DRD2) may be susceptibility factors for Parkinson's disease due to their influence on dopamine response and association with cigarette smoking, which is inversely related to risk of Parkinson's disease. Relations of TaqIA and TaqIB DRD2 genotypes with Parkinson's disease were investigated and tested for interactive effects with smoking and the monoamine oxidase B (MAO-B) intron 13 polymorphism previously found to be related to smoking. Study subjects were 152 cases of idiopathic Parkinson's disease and 231 controls. The smoking history of all genotyped subjects was known. Subjects of genotype B12 were more frequent among cases than controls (27% and 23.8%, respectively), and were more frequent among "ever smokers" than "never smokers", among controls (27.8% and 17.2%, respectively), although these associations were not statistically significant. Neither TaqIA or TaqIB genotypes modified the inverse relation of smoking and Parkinson's disease. When genotypes for DRD2 were considered in combination with genotypes for intron 13 of MAO-B, genotype combinations with high risk of Parkinson's disease were found; although the MAO-B/DRD2 interaction did not reach statistical significance after Bonferroni correction for multiple comparisons, these results are suggestive of a possible synergism between MAOB and DRD2 genes with respect to Parkinson's disease.
多巴胺D2受体(DRD2)的基因多态性可能是帕金森病的易感因素,因为它们会影响多巴胺反应并与吸烟相关,而吸烟与帕金森病风险呈负相关。研究了TaqIA和TaqIB DRD2基因型与帕金森病的关系,并测试了它们与吸烟以及先前发现与吸烟相关的单胺氧化酶B(MAO-B)内含子13多态性的交互作用。研究对象为152例特发性帕金森病患者和231名对照。所有进行基因分型的受试者的吸烟史均已知。病例组中B12基因型的受试者比对照组更常见(分别为27%和23.8%),在对照组的“曾经吸烟者”中比“从不吸烟者”更常见(分别为27.8%和17.2%),尽管这些关联无统计学意义。TaqIA或TaqIB基因型均未改变吸烟与帕金森病之间的负相关关系。当将DRD2基因型与MAO-B内含子13的基因型结合考虑时,发现了帕金森病高风险的基因型组合;尽管在进行多重比较的Bonferroni校正后,MAO-B/DRD2的相互作用未达到统计学意义,但这些结果提示MAO-B和DRD2基因在帕金森病方面可能存在协同作用。