Investigation of possible association between Ser9Gly polymorphism of the D3 dopaminergic receptor gene and response to typical antipsychotics in patients with schizophrenia
Keywords:
Pharmacogenetics, Dopamine, Association, Genetic polymorphism, SchizophreniaAbstract
Typical antipsychotics have a high affinity for dopamine receptors. It is therefore of interest to investigate such loci in pharmacogenetic studies on psychosis. We investigated the hypothesis that Ser9Gly polymorphism of the DRD3 gene may play a role in the differences in individual response to typical antipsychotics between schizophrenic patients. The sample was com- posed of 53 good responders and 59 poor ones. No significant differences between the good and poor responders were found in the allelic distribution (good responders: Ser9 61.32%, Gly9 38.67%; poor responders: Ser9 64.40%, Gly9 35.59%; odds ratio, OR = 0.88, 0.49 < OR < 1.56; 2 = 0.23, 1 degree of freedom, df, p = 0.63) and genotype distribution (good responders: Ser9/Ser9 37.73%, Ser9/Gly9 47.16%, Gly9/Gly9 15.09%; poor responders: Ser9/Ser9 42.37%, Ser9/Gly9 44.06%, Gly9/ Gly9 13.55%; 2 = 0.25, 2 df, p = 0.88). Nor was there any association with homozygosity (good responders: homozygous: 52.82%, hetero- zygous: 47.16%; poor responders: homozygous: 55.92%, heterozygous: 44.06%; odds ratio, OR = 0.88, 0.39 < OR < 1.99; 2 = 0.11, 1 df, p = 0.74). The results did not support the hypothesis that Ser9Gly polymorphism of the DRD3 gene influences the response to typical antipsychotics in our sample of schizophrenics.
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References
Meltzer HY. Treatment-resistant schizophrenia-the role of clozapine. Curr Med Res Opin. 1997;14(1):1-20.
Collier DA. Pharmacogenetics in psychosis. Drug News Per- spect. 2003;16(3):159-65.
Gupta S, Jain S, Brahmachari SK, Kukreti R. Pharmacogenom- ics: a path to predictive medicine for schizophrenia. Pharma- cogenomics. 2006;7(1):31-47.
Kane J, Honigfeld G, Singer J, Meltzer H. Clozapine for the treat- ment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry. 1988;45(9):789-96.
Lannfelt L, Sokoloff P, Martres MP, et al. Amino acid substitution in the dopamine D3 receptor as a useful polymorphism for inves- tigating psychiatric disorders. Psychiatr Genet. 1992;2:249-56.
Scharfetter J. Dopamine receptor polymorphisms and drug response in schizophrenia. Pharmacogenomics. 2001;2(3):251-61.
Jönsson EG, Flyckt L, Burgert E, et al. Dopamine D3 receptor gene Ser9Gly variant and schizophrenia: association study and meta-analysis. Psychiatr Genet. 2003;13(1):1-12.
Szekeres G, Keri S, Juhasz A, et al. Role of dopamine D3 recep- tor (DRD3) and dopamine transporter (DAT) polymorphism in cognitive dysfunctions and therapeutic response to atypical antipsychotics in patients with schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2004;124(1):1-5.
Scharfetter J. Pharmacogenetics of dopamine receptors and response to antipsychotic drugs in schizophrenia-an update. Pharmacogenomics. 2004;5(6):691-8.
Wilffert B, Zaal R, Brouwers JR. Pharmacogenetics as a tool in the therapy of schizophrenia. Pharm World Sci. 2005;27(1):20-30.
Masellis M, Basile VS, Ozdemir V, Meltzer HY, Macciardi FM, Kennedy JL. Pharmacogenetics of antipsychotic treatment: lessons learned from clozapine. Biol Psychiatry. 2000;47(3):252-66.
