Kumudini Nadella, Umai Addepally, Devi Yalavarthy Prameela, Naushad Shaik Mohammad, Mridula Rukmini, Borgohain Rupam, Kutala Vijay Kumar
Indian J Biochem Biophys. 2013 Oct;50(5):436-41.
In view of documented evidence demonstrating the association of dopaminergic metabolism and neurotransmission with Parkinson's disease (PD), a case-control study was conducted to investigate the impact of particular polymorphisms in the catechol O-methyl transferase (COMT) H108L, monoamine oxidase B (MAOB) int 13 A>G, dopamine transporter 1 (DAT1) A1215G, dopamine receptor D2 (DRD2) Taq1A, DRD2 Taq1B and DRD2 Taq1D genes on the susceptibility to PD. PCR-RFLP method was used for the genetic analysis. The COMT H108L polymorphism increased PD risk by 1.4-fold (95%CI: 1.02-1.98), whereas reduced risk was observed with MAOB int 13 A>G polymorphism (OR: 0.77, 95%CI: 0.51-0.99). Multifactor dimensionality reduction analysis showed gene-gene interactions between these two loci that resulted in loss of the protective role of MAOB G-allele in the presence of COMT L-allele. DAT1A1215G polymorphism in the exon 9 was not associated with PD. Individually, DRD2 polymorphisms showed null association. However, all-variant haplotype of DRD2 locus i.e. T-G-T haplotype showed 29.8-fold risk for PD compared to all-wild haplotype i.e., C-A-C haplotype (95%CI: 6.85-130.4). To conclude, genetic variants of COMT, MAOB and DRD2 loci modulate susceptibility to PD in South Indian subjects.
鉴于有文献证据表明多巴胺能代谢和神经传递与帕金森病（PD）相关，开展了一项病例对照研究，以调查儿茶酚-O-甲基转移酶（COMT）H108L、单胺氧化酶B（MAOB）内含子13 A>G、多巴胺转运体1（DAT1）A1215G、多巴胺受体D2（DRD2）Taq1A、DRD2 Taq1B和DRD2 Taq1D基因的特定多态性对PD易感性的影响。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法进行基因分析。COMT H108L多态性使PD风险增加1.4倍（95%置信区间：1.02-1.98），而MAOB内含子13 A>G多态性则降低了风险（比值比：0.77，95%置信区间：0.51-0.99）。多因素降维分析显示这两个基因座之间存在基因-基因相互作用，导致在存在COMT L等位基因的情况下MAOB G等位基因的保护作用丧失。外显子9中的DAT1 A1215G多态性与PD无关。单独来看，DRD2多态性显示无关联。然而，DRD2基因座的所有变异单倍型即T-G-T单倍型与所有野生型单倍型即C-A-C单倍型相比，显示出PD风险增加29.8倍（95%置信区间：6.85-130.4）。总之，COMT、MAOB和DRD2基因座的遗传变异调节了南印度人群对PD的易感性。
