Soumya Krishnamoorthy1, Roopa Rajan2, Moinak Banerjee3, Hardeep Kumar4, Gangadhara Sarma5, Syam Krishnan6, Sankara Sarma7, Asha Kishore8. 1. Comprehensive Care Centre for Movement Disorders, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Kerala, India. Electronic address: soumyamoorthy.k@gmail.com. 2. Comprehensive Care Centre for Movement Disorders, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Kerala, India. Electronic address: roops84@gmail.com. 3. Rajiv Gandhi Centre for Biotechnology, Kerala, India. Electronic address: mbanerjee@rgcb.res.in. 4. Comprehensive Care Centre for Movement Disorders, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Kerala, India. Electronic address: hardeep@sctimst.ac.in. 5. Comprehensive Care Centre for Movement Disorders, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Kerala, India. Electronic address: sarmasg24@yahoo.com. 6. Comprehensive Care Centre for Movement Disorders, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Kerala, India. Electronic address: drsyam@sctimst.ac.in. 7. Achutha Menon Centre for Health Science Studies, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Kerala, India. Electronic address: sarma@sctimst.ac.in. 8. Comprehensive Care Centre for Movement Disorders, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Kerala, India. Electronic address: asha@sctimst.ac.in.
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.
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 PDpatients (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 PDpatients 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.
Authors: Pengfei Yang; Joel S Perlmutter; Tammie L S Benzinger; John C Morris; Jinbin Xu Journal: Ageing Res Rev Date: 2019-11-22 Impact factor: 10.895
Authors: Esther A Pelzer; Barbara Dillenburger; Sophie Grundmann; Vladimir Iliaev; Sophie Aschenberg; Corina Melzer; Martin Hess; Gereon R Fink; Carsten Eggers; Marc Tittgemeyer; Lars Timmermann Journal: NPJ Parkinsons Dis Date: 2020-01-17
Authors: Maria Jose Catalan; Jose Antonio Molina-Arjona; Pablo Mir; Esther Cubo; Jose Matias Arbelo; Pablo Martinez-Martin Journal: J Neurol Date: 2018-03-20 Impact factor: 4.849