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Dopamine D3 receptor Ser9Gly variant is associated with impulse control disorders in Parkinson’s disease patients

Authors :
Gangadhara Sarma
Soumya Krishnamoorthy
Syam Krishnan
Hardeep Kumar
Moinak Banerjee
Asha Kishore
Roopa Rajan
Sankara P. Sarma
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.

Details

ISSN :
13538020
Volume :
30
Database :
OpenAIRE
Journal :
Parkinsonism & Related Disorders
Accession number :
edsair.doi.dedup.....c86a316e4f74121b4f17f26cc247d95a