DRD and GRIN2B polymorphisms and their association with the development of impulse control behaviour among Malaysian Parkinson's disease patients.

Shahidee Zainal Abidin,Azlina Ahmad Annuar,Alex Xuen Lee,Norlinah Mohamed Ibrahim,Mohd Hamdi Noor Abd Hamid,Shen Yang Lim,Eng Liang Tan,Shahrul Azmin,Nur Fadlina Pakarul Razy,Pike-See Cheah,King-Hwa Ling,Soon-Choy Chan,Nor Azian Abdul Murad,Ameerah Jaafar

doi:10.1186/s12883-015-0316-2

Abstract

BackgroundImpulse control disorder (ICD) and behaviours (ICB) represent a group of behavioural disorders that have become increasingly recognised in Parkinson’s disease (PD) patients who previously used dopaminergic medications, particularly dopamine agonists and levodopa. It has been suggested that these medications can lead to the development of ICB through the abnormal modulation of dopaminergic transmission and signalling in the mesocorticolimbic dopaminergic system. Several studies have reported an association between polymorphisms in the dopamine receptor (DRD) and N-methyl-D-aspartate 2B (GRIN2B) genes with the development of ICB in PD (PD-ICB) patients. Thus, this study aimed to investigate the association of selected polymorphisms within the DRD and GRIN2B genes with the development of ICB among PD patients using high resolution melt (HRM) analysis.MethodWe used high resolution melt (HRM) analysis to genotype 11 polymorphisms in 5 DRD genes [DRD1 (rs4532, rs4867798 and rs265981), DRD2 (ANKK1 rs1800497, rs104894220 and rs144999500), DRD3 (rs3732783 and rs6280), DRD4 (rs1800443), and DRD5 (rs144132215)] and 1 polymorphism in GRIN2B (rs7301328) in PD patients with (cases, n = 52) and without (controls, n = 39) ICB. Cases were obtained from two tertiary movement disorder centres [UKMMC (n = 9) and UMMC (n = 43)]. At both centres, the diagnosis of ICB was made using the QUIP questionnaire. Controls were recruited from PD patients who attended UKMMC and were found to be negative for ICB using the QUIP questionnaire.ResultsThe HRM analysis showed that 7 of 11 polymorphisms [DRD1 (rs4532, rs4867798, and rs265981), DRD2 (ANKK1 rs1800497), DRD3 (rs3732783 and rs6280), and GRIN2B (rs7301328)] exhibited a clear distinction between wild-type and variant alleles. Variants of DRD2/ANKK1 rs1800497 (OR = 3.77; 95% CI, 1.38-10.30; p = 0.0044), DRD1 rs4867798 (OR = 24.53; 95% CI, 1.68-357.28; p = 0.0054), DRD1 rs4532 (OR = 21.33; 95% CI, 1.97-230.64; p = 0.0024), and GRIN2B rs7301328 (OR = 25.07; 95% CI, 1.30-483.41; p = 0.0097) were found to be associated with an increased risk of developing ICB among PD patients.ConclusionOur findings suggest that polymorphisms in dopamine [DRD1 (rs4532 and rs4867798) and DRD2/ANKK1 rs1800497] and glutamate (GRIN2B rs7301328) receptor genes confer increased risk of ICB development among PD patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-015-0316-2) contains supplementary material, which is available to authorized users.

Highlights

Impulse control disorder (ICD) and behaviours (ICB) represent a group of behavioural disorders that have become increasingly recognised in Parkinson’s disease (PD) patients who previously used dopaminergic medications, dopamine agonists and levodopa
Variants of DRD2/ANKK1 rs1800497 (OR = 3.77; 95% confidence interval (CI), 1.38-10.30; p = 0.0044), DRD1 rs4867798 (OR = 24.53; 95% CI, 1.68-357.28; p = 0.0054), DRD1 rs4532 (OR = 21.33; 95% CI, 1.97-230.64; p = 0.0024), and GRIN2B rs7301328 (OR = 25.07; 95% CI, 1.30-483.41; p = 0.0097) were found to be associated with an increased risk of developing ICB among PD patients
Our findings suggest that polymorphisms in dopamine [DRD1 and DRD2/ ANKK1 rs1800497] and glutamate (GRIN2B rs7301328) receptor genes confer increased risk of ICB development among PD patients

Summary

Introduction

Impulse control disorder (ICD) and behaviours (ICB) represent a group of behavioural disorders that have become increasingly recognised in Parkinson’s disease (PD) patients who previously used dopaminergic medications, dopamine agonists and levodopa. Several studies have reported an association between polymorphisms in the dopamine receptor (DRD) and N-methyl-D-aspartate 2B (GRIN2B) genes with the development of ICB in PD (PD-ICB) patients. This study aimed to investigate the association of selected polymorphisms within the DRD and GRIN2B genes with the development of ICB among PD patients using high resolution melt (HRM) analysis. ICB/ICD has been increasingly recognized in PD patients who develop behaviour disorders, such as pathological gambling (5%), hypersexuality (3.6%), compulsive shopping (5.7%), and compulsive eating (4.3%). Patients can develop other subsyndromic ICB or ICD, such as compulsive medication use, punding, or hobbyism [3,4]. While some studies have shown that the development of ICB might be dose-dependent, others have suggested that genetic predisposition coupled with inherent ‘subconscious’ personality traits are the root cause of this problem [3,5]

Objectives

Methods

Results

Conclusion