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

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

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number59
JournalBMC Neurology
Volume15
Issue number1
DOIs
Publication statusPublished - 22 Apr 2015

Fingerprint

Behavior Control
Parkinson Disease
Genes
Disruptive, Impulse Control, and Conduct Disorders
Dopamine Agonists
Dopamine Receptors
Movement Disorders
Levodopa
N-Methylaspartate
Risk-Taking
Glutamic Acid
Dopamine
Alleles
Genotype

Keywords

  • DNA polymorphism
  • Dopamine receptor
  • High resolution melt analysis
  • N-methyl-D-aspartate 2B

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

DRD and GRIN2B polymorphisms and their association with the development of impulse control behaviour among Malaysian Parkinson's disease patients. / Zainal Abidin, Shahidee; Tan, Eng Liang; Chan, Soon Choy; Jaafar, Ameerah; Lee, Alex Xuen; Abd Hamid, Mohd Hamdi Noor; Abdul Murad, Nor Azian; Pakarul Razy, Nur Fadlina; Md. Rani, Shahrul Azmin; Ahmad Annuar, Azlina; Lim, Shen Yang; Cheah, Pike See; Ling, King Hwa; Mohamed Ibrahim, Norlinah.

In: BMC Neurology, Vol. 15, No. 1, 59, 22.04.2015.

Research output: Contribution to journalArticle

Zainal Abidin, S, Tan, EL, Chan, SC, Jaafar, A, Lee, AX, Abd Hamid, MHN, Abdul Murad, NA, Pakarul Razy, NF, Md. Rani, SA, Ahmad Annuar, A, Lim, SY, Cheah, PS, Ling, KH & 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, vol. 15, no. 1, 59. https://doi.org/10.1186/s12883-015-0316-2
Zainal Abidin, Shahidee ; Tan, Eng Liang ; Chan, Soon Choy ; Jaafar, Ameerah ; Lee, Alex Xuen ; Abd Hamid, Mohd Hamdi Noor ; Abdul Murad, Nor Azian ; Pakarul Razy, Nur Fadlina ; Md. Rani, Shahrul Azmin ; Ahmad Annuar, Azlina ; Lim, Shen Yang ; Cheah, Pike See ; Ling, King Hwa ; Mohamed Ibrahim, Norlinah. / DRD and GRIN2B polymorphisms and their association with the development of impulse control behaviour among Malaysian Parkinson's disease patients. In: BMC Neurology. 2015 ; Vol. 15, No. 1.
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abstract = "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.",
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author = "{Zainal Abidin}, Shahidee and Tan, {Eng Liang} and Chan, {Soon Choy} and Ameerah Jaafar and Lee, {Alex Xuen} and {Abd Hamid}, {Mohd Hamdi Noor} and {Abdul Murad}, {Nor Azian} and {Pakarul Razy}, {Nur Fadlina} and {Md. Rani}, {Shahrul Azmin} and {Ahmad Annuar}, Azlina and Lim, {Shen Yang} and Cheah, {Pike See} and Ling, {King Hwa} and {Mohamed Ibrahim}, Norlinah",
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TY - JOUR

T1 - DRD and GRIN2B polymorphisms and their association with the development of impulse control behaviour among Malaysian Parkinson's disease patients

AU - Zainal Abidin, Shahidee

AU - Tan, Eng Liang

AU - Chan, Soon Choy

AU - Jaafar, Ameerah

AU - Lee, Alex Xuen

AU - Abd Hamid, Mohd Hamdi Noor

AU - Abdul Murad, Nor Azian

AU - Pakarul Razy, Nur Fadlina

AU - Md. Rani, Shahrul Azmin

AU - Ahmad Annuar, Azlina

AU - Lim, Shen Yang

AU - Cheah, Pike See

AU - Ling, King Hwa

AU - Mohamed Ibrahim, Norlinah

PY - 2015/4/22

Y1 - 2015/4/22

N2 - 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.

AB - 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.

KW - DNA polymorphism

KW - Dopamine receptor

KW - High resolution melt analysis

KW - N-methyl-D-aspartate 2B

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