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

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Abstract

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.

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Acknowledgements

This research was supported by grants from ‘Financiadora de Estudos e Projetos’ (FINEP 01.08.01230.00), ‘Conselho Nacional de DesenvolvimentoCientífico e Tecnológico’ (CNPq) and ‘Fundo de Incentivo à Pesquisa’ (FIPE–HCPA). The funding sources had no role in study design, collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

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Authors and Affiliations

  1. Departamento de Genética, Instituto de Biociências, UFRGS, Porto Alegre, Brazil

    M Rieck, A F Schumacher-Schuh, V Altmann & M H Hutz

  2. Serviço de Neurologia, HCPA, R Ramiro Barcelos, Porto Alegre, Brazil

    A F Schumacher-Schuh & C R M Rieder

  3. Departamento de Estatística, Instituto de Matemática, UFRGS, Porto Alegre, Brazil,

    S M Callegari-Jacques

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  1. M Rieck
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  2. A F Schumacher-Schuh
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  4. S M Callegari-Jacques
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  5. C R M Rieder
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  6. M H Hutz
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Correspondence to M H Hutz.

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Rieck, M., Schumacher-Schuh, A., Altmann, V. et al. Association between DRD2 and DRD3 gene polymorphisms and gastrointestinal symptoms induced by levodopa therapy in Parkinson’s disease. Pharmacogenomics J 18, 196–200 (2018). https://doi.org/10.1038/tpj.2016.79

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  • DOI: https://doi.org/10.1038/tpj.2016.79

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