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帕金森病风险中的基因-基因和基因-环境相互作用。

Gene-gene and gene-environment interaction on the risk of Parkinson's disease.

作者信息

Singh Neeraj Kumar, Banerjee Basu Dev, Bala Kiran, Chhillar Mitrabasu, Chhillar Neelam

机构信息

Head, Department of Neurochemistry, Institute of Human Behaviour and Allied Sciences, Dilshad Garden, Delhi-110095, India.

出版信息

Curr Aging Sci. 2014;7(2):101-9. doi: 10.2174/1874609807666140805123621.

Abstract

BACKGROUND

Even with numerous studies the cause of Parkinson's disease (PD) remains elusive. It has been hypothesized that interactions between genetic and environmental factors may play an important role in the pathogenesis of PD.

OBJECTIVES

To examine the gene-gene and gene-environment interaction on PD risk with respect to gene polymorphism of cytochrome P450 2D6 (CYP2D6) and glutathione S-transferases pi 1 (GSTP1), organochlorine pesticides (OCPs) and metals.

METHODS

This study included 70 patients of PD and 100 age-matched controls. The restriction fragment length polymorphism was used for analysis of genetic polymorphism. OCPs and serum metal levels were estimated by using gas chromatography and an autoanalyser respectively.

RESULTS

The CYP2D64 mt and GSTP1 B allelic variants were significantly associated with increase in PD risk. We found a statistically significant difference in β -hexachlorocyclohexane (β-HCH), dieldrin, 1,1-dichloro-2,2-bis(pchlorophenyl) ethylene (pp'-DDE) and copper levels between the patients and controls. We found significantly high levels of β-HCH, dieldrin and pp'-DDE in the CYP2D64 mt allelic variants, β-HCH and pp'-DDE in the GSTP1B allelic variants and dieldrin in the GSTP1C allelic variants when comparing CYP2D64 non-mt, GSTP1 non-*B and GSTP1 non-*C allelic variants in patients of PD respectively.

CONCLUSION

This study demonstrates that the CYP2D6*4 and GSTP1 genes may be considered as candidate genes for PD and they may also interact with β- HCH, dieldrin and pp'-DDE to influence the risk for PD.

摘要

背景

尽管进行了大量研究,但帕金森病(PD)的病因仍不明确。据推测,遗传因素与环境因素之间的相互作用可能在PD的发病机制中起重要作用。

目的

探讨细胞色素P450 2D6(CYP2D6)和谷胱甘肽S-转移酶pi 1(GSTP1)基因多态性、有机氯农药(OCPs)和金属方面的基因-基因及基因-环境相互作用对PD风险的影响。

方法

本研究纳入70例PD患者和100例年龄匹配的对照。采用限制性片段长度多态性分析基因多态性。分别使用气相色谱法和自动分析仪测定OCPs和血清金属水平。

结果

CYP2D64 mt和GSTP1 B等位基因变异与PD风险增加显著相关。我们发现患者与对照之间的β-六氯环己烷(β-HCH)、狄氏剂、1,1-二氯-2,2-双(对氯苯基)乙烯(pp'-DDE)和铜水平存在统计学显著差异。在PD患者中,分别比较CYP2D64非mt、GSTP1非B和GSTP1非C等位基因变异时,发现CYP2D64 mt等位基因变异中的β-HCH、狄氏剂和pp'-DDE水平显著升高,GSTP1B等位基因变异中的β-HCH和pp'-DDE水平显著升高,GSTP1C等位基因变异中的狄氏剂水平显著升高。

结论

本研究表明,CYP2D6*4和GSTP1基因可能被视为PD的候选基因,它们也可能与β-HCH、狄氏剂和pp'-DDE相互作用,影响PD风险。

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