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 D(2) (DRD2), dopamine D(3) (DRD3), serotonin 2(a) (HTR2A), and serotonin 2(c) (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, chi(2) = 5.0) or AIP (P = 0.008, chi(2) = 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, chi(2) = 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.
Al Hadithy
Asmar F
AF
Department of Pharmacotherapy and Pharmaceutical Care, GUIDE, University of Groningen, Groningen, The Netherlands. a.f.y.al.hadithy@rug.nl
Wilffert
Bob
B
Stewart
Roy E
RE
Looman
Nicole M
NM
Bruggeman
Richard
R
Brouwers
Jacobus R
JR
Matroos
Glenn E
GE
van Os
Jim
J
Hoek
Hans W
HW
van Harten
Peter N
PN
D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001569:Benzodiazepines / Q000627:therapeutic use; D044383:Black People / Q000235:genetics*; D018680:Cholinergic Antagonists / Q000627:therapeutic use; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D018476:Hypokinesia / Q000188:drug therapy / Q000235:genetics*; D007297:Inpatients; D008297:Male; D008875:Middle Aged; D009127:Muscle Rigidity / Q000188:drug therapy / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000235:genetics*; D010597:Pharmacogenetics; D011954:Receptors, Dopamine / Q000235:genetics*; D011985:Receptors, Serotonin / Q000235:genetics*; D014202:Tremor / Q000188:drug therapy / Q000235:genetics*; D014900:West Indies / Q000208:ethnology
D014150:Antipsychotic Agents; D018680:Cholinergic Antagonists; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D001569:Benzodiazepines