Pharmacogenetics of parkinsonism, rigidity, rest tremor, and bradykinesia in African-Caribbean inpatients: Differences in association with dopamine and serotonin receptors

We studied the association between polymorphisms of genes coding for dopamine D2 (DRD2), dopamine D3 (DRD3), serotonin 2a (HTR2A), and serotonin 2c (HTR2C) receptors and Antipsychotic‐Induced Parkinsonism (AIP), rigidity, bradykinesia, and rest‐tremor in African‐Caribbeans treated with antipsychotic...

Full description

Saved in:
Bibliographic Details
Published in:American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2008-09, Vol.147B (6), p.890-897
Main Authors: Al Hadithy, Asmar F., Wilffert, Bob, Stewart, Roy E., Looman, Nicole M., Bruggeman, Richard, Brouwers, Jacobus R., Matroos, Glenn E., van Os, Jim, Hoek, Hans W., van Harten, Peter N.
Format: Article
Language:English
Subjects:
Adult
African Continental Ancestry Group - genetics
Aged
Antipsychotic Agents - therapeutic use
antipsychotics
Benzodiazepines - therapeutic use
Biological and medical sciences
bradykinesia
Cholinergic Antagonists - therapeutic use
Drug Resistance - genetics
Female
Gene Frequency
Genotype
Humans
Hypokinesia - drug therapy
Hypokinesia - genetics
Inpatients
Male
Medical genetics
Medical sciences
Middle Aged
Muscle Rigidity - drug therapy
Muscle Rigidity - genetics
Nervous system (semeiology, syndromes)
Nervous system as a whole
Neurology
Parkinsonian Disorders - drug therapy
Parkinsonian Disorders - genetics
parkinsonism
Pharmacogenetics
Receptors, Dopamine - genetics
Receptors, Serotonin - genetics
rigidity
tremor
Tremor - drug therapy
Tremor - genetics
West Indies - ethnology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We studied the association between polymorphisms of genes coding for dopamine D2 (DRD2), dopamine D3 (DRD3), serotonin 2a (HTR2A), and serotonin 2c (HTR2C) receptors and Antipsychotic‐Induced Parkinsonism (AIP), rigidity, bradykinesia, and rest‐tremor in African‐Caribbeans treated with antipsychotics. Polymorphisms of DRD2 (‐141CIns/Del, TaqIA, 957C > T), DRD3 (Ser9Gly), HTR2A (‐1438A > G, 102T > C, His452Tyr), and HTR2C (‐759C > T, Cys23Ser) genes were determined according to standard protocols. The Unified Parkinson Disease Rating Scale was used for the measurement of AIP, rigidity, bradykinesia, and rest‐tremor. Chi‐squared or Fisher's exact tests were applied for the association analyses. The t‐test was applied for continuous data. Ninety nine males and 27 females met the inclusion criteria (Schizophr Res 1996, 19:195). In males, but not in females, there were significant associations between ‐141CDel‐allele carriership (DRD2) and rigidity (Fisher's Exact Test: P = 0.021) and between 23Ser‐allele carriership (HTR2C) and bradykinesia (P = 0.026, χ2 = 5.0) or AIP (P = 0.008, χ2 = 7.1). Rest‐tremor was not associated with any of the polymorphisms studied. Analyses of the age, chlorpromazine equivalents, benztropine equivalents, the number of patients using anticholinergic medication, and the utilization patterns of the antipsychotic medication did not show statistically significant differences between patients with and without AIP, rigidity, bradykinesia, rest‐tremor. Conducting the analysis without gender stratification did not affect our findings considerably, except for the association between bradykinesia and 23Ser‐allele which failed to reach statistical significance in the total sample (P = 0.0646, χ2 = 3.41). Since AIPs subsymptoms (rigidity, bradykinesia, and rest‐tremor) may differ pharmacogenetically, our data strongly support symptom‐specific analysis of AIP. However, further research is warranted to confirm our findings. © 2008 Wiley‐Liss, Inc.
ISSN:1552-4841
1552-485X
DOI:10.1002/ajmg.b.30746