Department of Neurology, The Fifth Central Hospital of Tianjin, Binhai Hospital of Peking University, 40 Zhe Jiang Road of Binhai New Area, Tianjin, 300450, People's Republic of China.
Neurol Sci. 2021 Oct;42(10):4085-4094. doi: 10.1007/s10072-021-05509-3. Epub 2021 Aug 4.
Polymorphisms of the catechol-O-methyl transferase (COMT) or monoamine oxidase B (MAO-B) genes may affect the occurrence of dyskinesia in Parkinson's disease (PD) patients. However, the findings are inconsistent. Thus, we performed a meta-analysis to assess whether COMT and MAO-B genetic variants are associated with an increased incidence of levodopa-induced dyskinesia (LID) in PD patients.
A literature search of PubMed, Embase, and Cochrane Library was conducted to identify relevant studies published up to January 2021. The strength of the association between the polymorphisms and LID susceptibility was estimated by odds ratio (OR) and associated 95% confidence interval (CI). The pooled ORs were assessed in different genetic models.
Ten studies involving 2385 PD patients were included in the meta-analysis. Analysis of pooled ORs and 95% CIs suggested that the AA genotype of COMT(rs4680) was associated with LID (OR = 1.39, 95%CI: 1.02-1.89, P = 0.039) in the recessive model, and this correlation was more obvious in Brazilian samples in the analysis stratified by ethnicity. For the AG genotype of MAO-B(rs1799836), the pooled OR was 1.66 (95% CI: 1.04-2.65, P = 0.03) in patients with LID versus those without LID in the heterozygote model.
Our meta-analysis implicates the AA genotype of the COMT rs4680 polymorphism as potentially increasing the risk of LID in a recessive genetic model for PD patients. Furthermore, the AG genotype of the MAO-B rs1799836 polymorphism may influence the prevalence of LID in PD patients in the heterozygote model. However, further well-designed studies with larger PD patient cohorts are required to validate these results after adjusting for confounding factors.
儿茶酚-O-甲基转移酶(COMT)或单胺氧化酶 B(MAO-B)基因的多态性可能影响帕金森病(PD)患者发生运动障碍。然而,研究结果并不一致。因此,我们进行了一项荟萃分析,以评估 COMT 和 MAO-B 基因变异是否与 PD 患者左旋多巴诱导的运动障碍(LID)的发生率增加相关。
我们对 PubMed、Embase 和 Cochrane Library 进行了文献检索,以确定截至 2021 年 1 月发表的相关研究。使用比值比(OR)和相关 95%置信区间(CI)来估计遗传变异与 LID 易感性之间的关联强度。在不同的遗传模型中评估了合并的 OR。
纳入了 10 项研究,共 2385 名 PD 患者参与了荟萃分析。合并 OR 和 95%CI 的分析表明,COMT(rs4680)的 AA 基因型与 LID 相关(OR=1.39,95%CI:1.02-1.89,P=0.039),在按种族分层的分析中,这种相关性在巴西样本中更为明显。对于 MAO-B(rs1799836)的 AG 基因型,在杂合子模型中,LID 患者与无 LID 患者相比,合并 OR 为 1.66(95%CI:1.04-2.65,P=0.03)。
我们的荟萃分析表明,COMT rs4680 多态性的 AA 基因型可能在 PD 患者的隐性遗传模型中增加 LID 的风险。此外,MAO-B rs1799836 多态性的 AG 基因型可能影响 PD 患者中 LID 的患病率,在杂合子模型中。然而,需要进一步进行设计良好的、包含更大 PD 患者队列的研究,以在调整混杂因素后验证这些结果。