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Dopamine D3 receptor Ser9Gly variant is associated with impulse control disorders in Parkinson’s disease patients
- Source :
- Parkinsonism & Related Disorders. 30:13-17
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Introduction Impulse control disorders (ICD) are reported to occur at variable frequencies in different ethnic groups. Genetic vulnerability is suspected to underlie the individual risk for ICD. We investigated whether the allelic variants of dopamine (DRD3), glutamate (GRIN2B) and serotonin (HTR2A) receptors are linked to ICD in Indian Parkinson’s disease (PD) patients. Methods We conducted a prospective, case-control study which included PD patients (70 with ICD, 100 without ICD categorized after direct psychiatric interview of patient and caregiver) and 285 healthy controls. Single nucleotide polymorphism (SNP) variants of DRD3 p.S9G (rs6280), GRIN2B c.2664C>T (rs1806201) and HTR2A c.102T>C (rs6313) were genotyped. Results Multivariate regression analysis revealed that DRD3 p.Ser9Gly (rs6280) heterozygous variant CT (OR = 2.22, 95% CI: 1.03–4.86, p = 0.041), higher daily Levodopa equivalent doses (LED) of drugs (for 100 mg LED, OR = 1.14, 95% CI: 1.01–1.29, p = 0.041), current dopamine agonist but not Levodopa use (OR = 2.16, 95% CI: 1.03–4.55, p = 0.042) and age of onset of motor symptoms under 50 years (OR 2.09, 95% CI: 1.05–4.18, p = 0.035) were independently associated with ICD. Conclusion DRD3 p.Ser9Gly (rs6280) CT genotype is associated with ICD in Indian PD patients and this association is novel. Enhanced D3 receptor affinity due to gain-of-function conferred by the glycine residues could impair reward-risk assessment in the mesolimbic system and contribute to development of impulsive behaviour, in carriers of this genotype.
- Subjects :
- Adult
Male
0301 basic medicine
medicine.medical_specialty
Levodopa
Parkinson's disease
Genotype
Rs6313
Pharmacology
Polymorphism, Single Nucleotide
Gastroenterology
Dopamine agonist
03 medical and health sciences
0302 clinical medicine
Asian People
Dopamine receptor D3
Internal medicine
medicine
Humans
Genetic Predisposition to Disease
Prospective Studies
Aged
Pramipexole
Receptors, Dopamine D3
Parkinson Disease
Middle Aged
medicine.disease
Disruptive, Impulse Control, and Conduct Disorders
030104 developmental biology
Ropinirole
Neurology
Case-Control Studies
Dopamine Agonists
Female
Neurology (clinical)
Geriatrics and Gerontology
Age of onset
Psychology
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 13538020
- Volume :
- 30
- Database :
- OpenAIRE
- Journal :
- Parkinsonism & Related Disorders
- Accession number :
- edsair.doi.dedup.....c86a316e4f74121b4f17f26cc247d95a