The influence of SLC6A3 and DRD2 polymorphisms on levodopa-therapy in patients with sporadic Parkinson's disease

J Pharm Pharmacol. 2019 Feb;71(2):206-212. doi: 10.1111/jphp.13031. Epub 2018 Oct 23.

Abstract

Objectives: The aim of this study was to evaluate a possible relationship between DRD2/ANKK1 (rs1800497) and SLC6A3/DAT1 (rs28363170) gene polymorphisms with the response to levodopa (L-DOPA)-therapy in patients with Parkinson's disease (PD).

Methods: One hundred and ninety-five patients with idiopathic PD were investigated. Patients were genotyped for rs1800497 and rs28363170 polymorphisms using PCR-RFLP. Logistic regression was performed to assess the association of polymorphisms with the occurrence of the chronic complications of L-DOPA therapy.

Key findings: Our results showed association between the occurrence of dyskinesia with an increased greater disease severity (P = 0.007), higher L-DOPA dose (P = 0.007) and use of dopamine agonist (P = 0.020). Moreover, there were significant protective effects for age (P = 0.004) and male subjects (P = 0.006).

Conclusions: Clinical and demographic characteristics of Brazilian PD patients and differences in DRD2 and DAT1 genes may to determine individual variations in the therapeutic response to L-DOPA in the Brazilian PD patients.

Keywords: Parkinson's disease; dopamine transporter; genetic polymorphism; pharmacogenetics; side effects.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Antiparkinson Agents / administration & dosage
  • Antiparkinson Agents / adverse effects
  • Antiparkinson Agents / pharmacology
  • Brazil
  • Dopamine Plasma Membrane Transport Proteins / genetics*
  • Dose-Response Relationship, Drug
  • Female
  • Genotype
  • Humans
  • Levodopa / administration & dosage
  • Levodopa / adverse effects
  • Levodopa / pharmacology*
  • Logistic Models
  • Male
  • Middle Aged
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / genetics
  • Parkinson Disease / physiopathology
  • Polymorphism, Genetic
  • Protein Serine-Threonine Kinases / genetics
  • Receptors, Dopamine D2 / genetics*
  • Severity of Illness Index
  • Sex Factors
  • Treatment Outcome

Substances

  • Antiparkinson Agents
  • DRD2 protein, human
  • Dopamine Plasma Membrane Transport Proteins
  • Receptors, Dopamine D2
  • SLC6A3 protein, human
  • Levodopa
  • ANKK1 protein, human
  • Protein Serine-Threonine Kinases