Rieck M, Schumacher-Schuh A F, Altmann V, Callegari-Jacques S M, Rieder C R M, Hutz M H
Departamento de Genética, Instituto de Biociências, UFRGS, Porto Alegre, Brazil.
Serviço de Neurologia, HCPA, R Ramiro Barcelos, Porto Alegre, Brazil.
Pharmacogenomics J. 2018 Jan;18(1):196-200. doi: 10.1038/tpj.2016.79. Epub 2016 Oct 25.
Levodopa is the most used drug to treat motor symptoms in Parkinson's disease (PD). However, dopaminergic side effects such as nausea and vomiting may occur. Several evidences indicate a major role for dopamine receptors D2 (DRD2) and D3 (DRD3) in emetic activity. The aim of this study was to investigate the relationship of DRD2 rs1799732 and DRD3 rs6280 gene polymorphisms with gastrointestinal (GI) symptoms induced by levodopa in PD patients. Two hundred and seventeen PD patients on levodopa therapy were investigated. DRD2 rs1799732 and DRD3 rs6280 polymorphisms were genotyped by PCR-based methods. Multiple Poisson regression method with robust variance estimators was performed to assess the association between polymorphisms and gastrointestinal symptoms. The analyses showed that DRD2 Ins/Ins (prevalence ratio (PR)=2.374, 95% confidence interval (CI): 1.105-5.100; P=0.027) and DRD3 Ser/Ser genotypes (PR=1.677, 95% CI 1.077-2.611; P=0.022) were independent and predictors of gastrointestinal symptoms associated with levodopa therapy. Despite all the efforts to alleviate GI symptoms, this adverse effect still occurs in PD patients. Pharmacogenetic studies of GI symptoms induced by levodopa therapy have the potential to display new ways to better understand the molecular mechanisms involved in these side effects.
左旋多巴是治疗帕金森病（PD）运动症状最常用的药物。然而，可能会出现恶心和呕吐等多巴胺能副作用。多项证据表明多巴胺受体D2（DRD2）和D3（DRD3）在催吐活动中起主要作用。本研究的目的是调查DRD2 rs1799732和DRD3 rs6280基因多态性与PD患者左旋多巴诱发的胃肠道（GI）症状之间的关系。对217例接受左旋多巴治疗的PD患者进行了调查。采用基于聚合酶链反应（PCR）的方法对DRD2 rs1799732和DRD3 rs6280多态性进行基因分型。采用具有稳健方差估计量的多重泊松回归方法评估多态性与胃肠道症状之间的关联。分析表明，DRD2 Ins/Ins基因型（患病率比（PR）=2.374，95%置信区间（CI）：1.105 - 5.100；P = 0.027）和DRD3 Ser/Ser基因型（PR = 1.677，95% CI 1.077 - 2.611；P = 0.022）是与左旋多巴治疗相关的胃肠道症状的独立预测因素。尽管为缓解胃肠道症状付出了种种努力，但这种不良反应在PD患者中仍然会出现。左旋多巴治疗诱发的胃肠道症状的药物遗传学研究有可能展示新的方法，以便更好地理解这些副作用所涉及的分子机制。
