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

Abstract

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.

Lack of association between antipsychotic‐induced Parkinsonism or its subsymptoms and rs4606 SNP of RGS2 gene in African‐Caribbeans and the possible role of the medication: The Curacao extrapyramidal syndromes study X

“…Correction for the possible effects of these SNPs is indicated in our study, because these SNPs have been associated with AIP, rigidity, and bradykinesia in the same African-Caribbean sample (Al Hadithy et al, 2008). There were no differences in age or in the utilization patterns of antipsychotics, anticholinergics, and benzodiazepines and the lack of association is therefore not likely to be caused by these potential confounders.…”

“…Several risk factors have been suggested to predispose to AIP such as old age, female gender, high antipsychotic dose, and hereditary predisposition (Al Hadithy et al, 2008;Caligiuri et al, 1999;Hirose, 2006;Jabs et al, 2003).…”

Association of two DRD2 gene polymorphisms with acute and tardive antipsychotic-induced movement disorders in young Caucasian patients

“…Five studies so far have reported associations with acute antipsychotic-induced MD without specifying the MD under study (Al-Janabi et al 2009;Greenbaum et al 2007Greenbaum et al , 2009Gunes et al 2007Gunes et al , 2008. To our knowledge, only one candidate study has reported significant results with akathisia specifically (Eichhammer et al 2000) and only one with parkinsonism (Al Hadithy et al 2008) both in an older sample with a mean age of 40 and 49 years, respectively. The affinities for multiple receptors of second-generation antipsychotics, other than the prevailing affinity for the DRD2 receptor of the first-generation antipsychotics, may be responsible for the differing pharmacogenetic associations found in our group of patients.…”

“…The reported association between functional DRD2 promoter allele −141C Del and tardive dyskinesia was not found previously (de Leon et al 2005;Hori et al 2001; Kaiser et al 2002;Zai et al 2007) but an association was found between this promoter allele and antipsychotic-induced parkinsonism (Al Hadithy et al 2008). This may be of clinical interest as antipsychotic-induced parkinsonism has been shown to be a risk factor for the development of tardive dyskinesia (Kane 2006;Tenback et al 2006Tenback et al , 2009.…”

Pharmacogenetic Research Activity in Central America and the Caribbean: A Systematic Review

“…Cardiovascular ranked second with Puerto Rico [25][26][27][62][63][64] and Costa Rica [11,15,16,50,60,65,113] as the main contributors. Neurology/psychiatry placed third with a greater contribution of the Caribbean islands of Curaçao [85,86,110], Martinique [87], Jamaica [56,61], Cuba [82] and Puerto Rico [35,36,66,95] (Figure 3). These results are in agreement with the global trend of scientific research in these areas [10].…”