Association between DRD2 and DRD3 gene polymorphisms and gastrointestinal symptoms induced by levodopa therapy in Parkinson’s disease

• Published in: The pharmacogenomics journal 2018-01, Vol.18 (1), p.196-200
• Main Authors: Rieck, M, Schumacher-Schuh, A F, Altmann, V, Callegari-Jacques, S M, Rieder, C R M, Hutz, M H
• Format: Article
• Language: English
• Subjects: 631/208/205; 631/208/721; Aged; Analysis; Biomedical and Life Sciences; Biomedicine; Complications and side effects; consensus-article; Dopamine D2 receptors; Dopamine D3 receptors; Dopamine receptors; Dosage and administration; Drug therapy; Female; Gastrointestinal Diseases - chemically induced; Gastrointestinal Diseases - genetics; Gastrointestinal symptoms; Gene Expression; Genetic aspects; Genetic polymorphisms; Genetic Predisposition to Disease - genetics; Genotype; Genotypes; Human Genetics; Humans; L-dopa; Levodopa; Levodopa - adverse effects; Levodopa - therapeutic use; Male; Molecular modelling; Movement disorders; Nausea; Neurodegenerative diseases; Oncology; Parkinson disease; Parkinson Disease - drug therapy; Parkinson Disease - genetics; Parkinson's disease; Pharmacotherapy; Physiological aspects; Poisson density functions; Polymorphism, Genetic - genetics; Psychopharmacology; Receptors, Dopamine D2 - genetics; Receptors, Dopamine D3 - genetics; Side effects; Studies; Vomiting
• ISSN: 1470-269X; 1473-1150
• DOI: 10.1038/tpj.2016.79

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.