Polymorphism in environment responsive genes and association with Parkinson disease
Polymorphism in environment responsive genes and association with Parkinson disease
复制标题
DOI：
10.1007/s11010-008-9728-2
复制
发表时间：
2008-05-01
影响因子：
4.3
通讯作者：
Parmar, Devendra
中科院分区：
文献类型：
--
作者：
Singh, Madhu;Khan, Anwar J.;Parmar, Devendra
本病例对照研究旨在探讨编码参与中毒-解毒和多巴胺能通路的蛋白质的基因多态性与帕金森病（PD）易感性之间的关系。本研究纳入了70例PD患者和100例属于同一地理位置和同一种族的健康对照。采用PCR-RFLP和等位基因特异性PCR方法进行基因型鉴定。多因素Logistic回归分析显示，细胞色素P4502 D 6 *4（CYP 2D 6 *4）、CYP 2 E1 * 5 B（RsaI）多态性杂合基因型和CYP 2 E1 *6（Dra 1）纯合突变基因型在PD患者中的比例高于对照组。携带谷胱甘肽S-转移酶T1（GSTT 1）缺失或GSTP 1纯合变异基因型的患者风险也增加。观察到单胺氧化酶-B（MAO-B）变异等位基因G与PD显著相关，而对照组和PD病例之间锰超氧化物歧化酶（MnSOD）、多巴胺受体-D2（DRD 2）和多巴胺转运蛋白（DAT）基因的基因型和等位基因频率无差异。以其相应位点上存在两种变异基因型为特征的基因型组合显示，患者中GSTT 1 null和MnSOD（-9Val）或GST null和MAOB-G或CYP 2 E1 * 5 B和MAO-B-AG或CYP 2 E1 * 5 B和DRD 2（Taq 1A-het）基因型的四种组合显示出数倍高的PD风险，且与PD风险显著相关。我们的数据表明，参与解毒和多巴胺调节的基因多态性可能会调节PD的易感性，并可能是PD发病机制中的重要危险因素。
Attempts were made in the present case-control study to investigate the association of polymorphism in the genes encoding proteins involved in toxication-detoxication and dopaminergic pathways and susceptibility to Parkinson's disease (PD). Seventy patients suffering from PD and one hundred healthy controls belonging to the same geographical location and same ethnicity were included in the study. PCR-RFLP and allele-specific PCR-based methodology were used to identify the genotypes. Multivariate logistic regression analysis revealed that heterozygous genotypes of cytochrome P4502D6*4(CYP2D6*4), CYP2E1*5B (RsaI) polymorphism and homozygous mutant genotypes of CYP2E1*6 (Dra1) were found to be overrepresented in PD cases when compared to the controls. Risk was also found to be increased in patients carrying glutathione S-transferase T1 (GSTT1) null or homozygous variant genotypes of GSTP1. Significant association was observed for monoamine oxidase-B(MAO-B) variant allele G and PD, whereas no difference in genotype and allele frequencies was observed for manganese-superoxide dismutase (MnSOD), dopamine receptor-D2(DRD2), and dopamine transporter (DAT) genes between controls and PD cases. Genotype combinations characterized by the presence of two variant genotypes on their corresponding loci revealed that four combinations of GSTT1 null and MnSOD(-9Val) or GST null and MAOB-G or CYP2E1*5B and MAO-B-AG or CYP2E1*5B and DRD2 (Taq1A-het) genotypes in the patients exhibited severalfold higher and significant association with risk to PD. Our data suggest that polymorphism in the genes involved in detoxification and dopamine regulation may modulate the susceptibility to PD and could be important risk factors in the pathogenesis of PD.