Gene-environment interactions in parkinsonism and Parkinson's disease: the Geoparkinson study
Gene-environment interactions in parkinsonism and Parkinson's disease: the Geoparkinson study
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DOI：
10.1136/oem.2006.032078
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发表时间：
2007-10-01
影响因子：
4.9
通讯作者：
Felice, A.
中科院分区：
文献类型：
--
作者：
Dick, F. D.;De Palma, G.;Felice, A.
目的：调查协会帕金森氏病（PD）和帕金森综合征与多态性基因，影响代谢的外来化学物质或多巴胺，并寻求证据的基因-环境相互作用的影响，修改risk.Methods：959例流行的帕金森氏症（767 PD）和1989年控制在5个欧洲中心的病例对照研究。职业卫生学家估计了溶剂、杀虫剂和金属（铁、铜、锰）的平均年暴露强度，而对疾病状况一无所知。对CYP 2D 6、PON 1、GSTM 1、GSTT 1、GSTM 3、GSTP 1、NQO 1、CYP 1B 1、MAO-A、MAO- B、SOD 2、EPHX、DAT 1、DRD 2和NAT 2进行基因分型。结果进行了分析，采用多元Logistic回归调整的关键confers.Results：有一个温和的，但显着的关联MAO-A多态性在男性和疾病的风险（G与T，OR 1.30，95%CI 1.02至1.66，调整）。大多数基因-环境分析没有显示出显著的交互作用。有可能的GSTM 1无效基因型和溶剂暴露之间的相互作用的影响（这是更强的，仅限于PD病例时）。结论：许多小的研究报告遗传多态性和PD之间的关联。很少有人研究基因与环境的相互作用.这项大型研究足以检验这些方面。大量暴露于溶剂的GSTM 1缺失受试者出现PD的风险增加。没有足够的证据表明其他基因-环境组合研究了改良的疾病风险，表明它们对PD负担的贡献很小。
Objectives: To investigate associations of Parkinson's disease (PD) and parkinsonian syndromes with polymorphic genes that influence metabolism of either foreign chemical substances or dopamine and to seek evidence of gene-environment interaction effects that modify risk.Methods: A case-control study of 959 prevalent cases of parkinsonism (767 with PD) and 1989 controls across five European centres. Occupational hygienists estimated the average annual intensity of exposure to solvents, pesticides and metals, (iron, copper, manganese), blind to disease status. CYP2D6, PON1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, CYP1B1, MAO-A, MAO- B, SOD 2, EPHX, DAT1, DRD2 and NAT2 were genotyped. Results were analysed using multiple logistic regression adjusting for key confounders.Results: There was a modest but significant association between MAO-A polymorphism in males and disease risk (G vs T, OR 1.30, 95% Cl 1.02 to 1.66, adjusted). The majority of gene-environment analyses did not show significant interaction effects. There were possible interaction effects between GSTM1 null genotype and solvent exposure (which were stronger when limited to PD cases only).Conclusions: Many small studies have reported associations between genetic polymorphisms and PD. Fewer have examined gene- environment interactions. This large study was sufficiently powered to examine these aspects. GSTM1 null subjects heavily exposed to solvents appear to be at increased risk of PD. There was insufficient evidence that the other gene- environment combinations investigated modified disease risk, suggesting they contribute little to the burden of PD.