Lack of association between DRD3 gene polymorphism and response to clozapine in Turkish schizoprenia patients

Barlas, İbrahim Ömer; Çetin, Mesut; Semiz, Ümit Başar; Başoğlu, Cengiz; Ay, Mustafa; Herken, Hasan; Uzun, Özcan

doi:10.1002/ajmg.b.30770

Cited by 31 publications

(15 citation statements)

References 45 publications

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“…99 Two studies analyzed the Ser9Gly polymorphism in DRD3, and the Ser/Ser genotype was found to be more frequent among non-responders to clozapine, 27,28 but other studies failed to replicate these findings. [100][101][102][103][104][105][106] The importance of Ser9Gly was confirmed in a meta-analysis, where significant differences were found when the DRD3 Ser9 allele or the Ser/Ser genotype were compared between responders and non-responders to clozapine in a sample of 233 schizophrenia patients. 107 However, a more recent meta-analysis with a much larger sample size (n=758) reported a negative but consistent trend for the DRD3 Ser9 allele and poor clozapine response.…”

Section: -98mentioning

confidence: 81%

Pharmacogenetics in schizophrenia: a review of clozapine studies

Kohlrausch

2013

Rev. Bras. Psiquiatr.

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Objectives: Clozapine is quite effective to treat schizophrenia, but its use is complicated by several factors. Although many patients respond to antipsychotic therapy, about 50% of them exhibit inadequate response, and ineffective medication trials may entail weeks of unremitted illness, potential adverse drug reactions, and treatment nonadherence. This review of the literature sought to describe the main pharmacogenetic studies of clozapine and the genes that potentially influence response to treatment with this medication in schizophrenics. Methods: We searched the PubMed database for studies published in English in the last 20 years using keywords related to the topic. Results and Conclusions: Our search yielded 145 studies that met the search and selection criteria. Of these, 21 review articles were excluded. The 124 studies included for analysis showed controversial results. Therefore, efforts to identify key gene mechanisms that will be useful in predicting clozapine response and side effects have not been fully successful. Further studies with new analysis approaches and larger sample sizes are still required.

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Section: -98mentioning

confidence: 81%

Pharmacogenetics in schizophrenia: a review of clozapine studies

Kohlrausch

2013

Rev. Bras. Psiquiatr.

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“…Several studies have examined the association between this polymorphism and efficacy (227, 238, 250, 284, 316, 334, 339, 400, 418, 420, 439, 446, 449) and adverse effects like TD (211, 215, 223, 228, 237, 242, 244, 252, 257, 278, 286, 375, 401, 416, 443, 452, 473, 492). A mega-analysis of combined data from several studies on 780 patients (276) suggested the Gly9 allele conferred a small, but significant, increase in risk of TD.…”

Section: Antipsychoticsmentioning

confidence: 99%

The Promise and Reality of Pharmacogenetics in Psychiatry

Zandi

Judy

2010

Psychiatric Clinics of North America

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“…A computer search on the United States National Library of Medicine and National Institutes of Health online search engine database, PubMed, was performed in order to identify all papers published up to 15 October 2009 on association studies related to the DRD3 Ser9Gly polymorphism and CLZ response. Six studies were identified: Shaikh et al, 57 Gaitonde et al, 58 Malhotra et al, 59 Scharfetter et al, 60 Arranz et al 61 and Barlas et al 62 However, Ser9Gly genotype data for Gaitonde et al 58 and Arranz et al 61 were not available from their respective publications. These data were obtained directly from the authors.…”

Section: )mentioning

confidence: 99%

Effect of dopamine D3 receptor gene polymorphisms and clozapine treatment response: exploratory analysis of nine polymorphisms and meta-analysis of the Ser9Gly variant

et al. 2009

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D2 blockade has been implicated in having a central role in antipsychotic response. However, treatment refractoriness, in spite of complete D2 blockade, as well as the efficacy of clozapine (CLZ) in a portion of this patient population, indicates the involvement of other factors as well. Several lines of evidence suggest a role for D3. Furthermore, an earlier meta-analysis by Jönsson et al. (2003) (n ¼ 233) suggested a role for genetic variation in the D3 gene. Relevant to this study, Jönsson et al. found the Ser allele of the D3 serine-to-glycine substitution at amino acid position 9 (Ser9Gly) polymorphism to be associated with worse CLZ response compared with the Gly allele. In this study, we attempt to validate these findings by performing a meta-analysis in a much larger sample (n ¼ 758). Eight other variants were also tested in our own sample to explore the possible effect of other regions of the gene. We report a negative but consistent trend across individual studies in our meta-analysis for the DRD3 Ser allele and poor CLZ response. A possible minor role for this single-nucleotide polymorphism cannot be disregarded, as our sample size may have been insufficient. Other DRD3 variants and haplotypes of possible interest were also identified for replication in future studies.

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Lack of association between DRD3 gene polymorphism and response to clozapine in Turkish schizoprenia patients

Cited by 31 publications

References 45 publications

Pharmacogenetics in schizophrenia: a review of clozapine studies

Pharmacogenetics in schizophrenia: a review of clozapine studies

The Promise and Reality of Pharmacogenetics in Psychiatry

Effect of dopamine D3 receptor gene polymorphisms and clozapine treatment response: exploratory analysis of nine polymorphisms and meta-analysis of the Ser9Gly variant

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