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

Background: 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, particularly dopamine agonists and levodopa. It has been suggest...

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Main Authors:	Zainal Abidin, S., Tan, E.L., Chan, S.C., Jaafar, Ameerah, Lee, A.X., Abd Hamid, M.H.N., Abdul Murad, N.A., Pakarul Razy, N.F., Azmin, S., Ahmad-Annuar, Azlina, Lim, Shen Yang, Cheah, P.S., Ling, K.H., Mohamed Ibrahim, N.
Format:	Article
Published:	BioMed Central 2015
Subjects:	R Medicine
Online Access:	http://eprints.um.edu.my/19294/ https://doi.org/10.1186/s12883-015-0316-2
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spelling	my.um.eprints.192942020-02-05T04:55:26Z http://eprints.um.edu.my/19294/ DRD and GRIN2B polymorphisms and their association with the development of impulse control behaviour among Malaysian Parkinson’s disease patients Zainal Abidin, S. Tan, E.L. Chan, S.C. Jaafar, Ameerah Lee, A.X. Abd Hamid, M.H.N. Abdul Murad, N.A. Pakarul Razy, N.F. Azmin, S. Ahmad-Annuar, Azlina Lim, Shen Yang Cheah, P.S. Ling, K.H. Mohamed Ibrahim, N. R Medicine Background: 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, 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. Method: We 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. Results: The 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. Conclusion: Our 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. BioMed Central 2015 Article PeerReviewed Zainal Abidin, S. and Tan, E.L. and Chan, S.C. and Jaafar, Ameerah and Lee, A.X. and Abd Hamid, M.H.N. and Abdul Murad, N.A. and Pakarul Razy, N.F. and Azmin, S. and Ahmad-Annuar, Azlina and Lim, Shen Yang and Cheah, P.S. and Ling, K.H. and Mohamed Ibrahim, N. (2015) DRD and GRIN2B polymorphisms and their association with the development of impulse control behaviour among Malaysian Parkinson’s disease patients. BMC Neurology, 15 (1). p. 59. ISSN 1471-2377 https://doi.org/10.1186/s12883-015-0316-2 doi:10.1186/s12883-015-0316-2
institution	Universiti Malaya
building	UM Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Malaya
content_source	UM Research Repository
url_provider	http://eprints.um.edu.my/
topic	R Medicine
spellingShingle	R Medicine Zainal Abidin, S. Tan, E.L. Chan, S.C. Jaafar, Ameerah Lee, A.X. Abd Hamid, M.H.N. Abdul Murad, N.A. Pakarul Razy, N.F. Azmin, S. Ahmad-Annuar, Azlina Lim, Shen Yang Cheah, P.S. Ling, K.H. Mohamed Ibrahim, N. DRD and GRIN2B polymorphisms and their association with the development of impulse control behaviour among Malaysian Parkinson’s disease patients
description	Background: 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, 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. Method: We 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. Results: The 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. Conclusion: Our 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.
format	Article
author	Zainal Abidin, S. Tan, E.L. Chan, S.C. Jaafar, Ameerah Lee, A.X. Abd Hamid, M.H.N. Abdul Murad, N.A. Pakarul Razy, N.F. Azmin, S. Ahmad-Annuar, Azlina Lim, Shen Yang Cheah, P.S. Ling, K.H. Mohamed Ibrahim, N.
author_facet	Zainal Abidin, S. Tan, E.L. Chan, S.C. Jaafar, Ameerah Lee, A.X. Abd Hamid, M.H.N. Abdul Murad, N.A. Pakarul Razy, N.F. Azmin, S. Ahmad-Annuar, Azlina Lim, Shen Yang Cheah, P.S. Ling, K.H. Mohamed Ibrahim, N.
author_sort	Zainal Abidin, S.
title	DRD and GRIN2B polymorphisms and their association with the development of impulse control behaviour among Malaysian Parkinson’s disease patients
title_short	DRD and GRIN2B polymorphisms and their association with the development of impulse control behaviour among Malaysian Parkinson’s disease patients
title_full	DRD and GRIN2B polymorphisms and their association with the development of impulse control behaviour among Malaysian Parkinson’s disease patients
title_fullStr	DRD and GRIN2B polymorphisms and their association with the development of impulse control behaviour among Malaysian Parkinson’s disease patients
title_full_unstemmed	DRD and GRIN2B polymorphisms and their association with the development of impulse control behaviour among Malaysian Parkinson’s disease patients
title_sort	drd and grin2b polymorphisms and their association with the development of impulse control behaviour among malaysian parkinson’s disease patients
publisher	BioMed Central
publishDate	2015
url	http://eprints.um.edu.my/19294/ https://doi.org/10.1186/s12883-015-0316-2
_version_	1662755157558951936
score	13.211869

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

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