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

Yazan: admin Tarih: Nis 22nd, 2009 | Kategori:: Kategorilenmemiş
I. Omer Barlas 1 *, Mesut Cetin 2, M. Emin Erdal 1, Umit B. Semiz 2, Cengiz Basoglu 2, M. Ertan Ay 1, Hasan Herken 3, Ozcan Uzun 4
1Department of Medical Biology and Genetics, Medical Faculty of Mersin University, Mersin, Turkey
2Department of Psychiatry, GATA Haydarpasa Training Hospital, Istanbul, Turkey
3Department of Psychiatry, Medical Faculty of Pamukkale University, Denizli, Turkey
4Department of Psychiatry, Gulhane Military Medical Academy, Ankara, Turkey
email: I. Omer Barlas (iobarlas@gmail.com)

*Correspondence to I. Omer Barlas, Department of Medical Biology and Genetics, Medical Faculty of Mersin University, Mersin, Turkey.

Please cite this article as follows: Barlas IO, Cetin M, Erdal ME, Semiz UB, Basoglu C, Ay ME, Herken H, Uzun O. 2008. Lack of Association Between DRD3 Gene Polymorphism and Response to Clozapine in Turkish Schizoprenia Patients. Am J Med Genet Part B 150B:56-60.

Keywords
schizophrenia • clozapine • dopamine D3 receptor gene (DRD3) • polymorphism • association
Abstract
It is hypothesized that molecular components of dopaminergic system, especially the dopamine D3 receptor gene (DRD3), may play a crucial role in the pathophysiology of schizophrenia, because it is abundant in the limbic system of the brain and it binds antipsychotic drugs. Several groups attempted to find an association between a serine-to-glycine polymorphism of the DRD3 gene (Ser9Gly) and schizophrenia; however, the results were inconsistent. In this study, we aimed to investigate the relationship of the Serine/Glycine polymorphism of the DRD3 gene with therapeutic response to clozapine treatment between Turkish schizophrenia patients (N = 92) and healthy controls (N = 100). Genotype groups were comparable in BPRS, SAPS, SANS analysis of response to clozapine. Our results suggest that an association between the Ser/Gly polymorphism of DRD3 gene and response to clozapine in Turkish schizophrenia patients is unlikely to exist. © 2008 Wiley-Liss, Inc.
Received: 10 December 2007; Accepted: 26 March 2008

Digital Object Identifier (DOI)

10.1002/ajmg.b.30770  About DOI


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Paraoxonase-1 55/192 genotypes in schizophrenic patients and their relatives in Turkish population.

Yazan: admin Tarih: Ara 10th, 2008 | Kategori:: Kategorilenmemiş

Psychiatr Genet. 2008 Dec;18(6):289-94

Kucukali CI, Aydin M, Ozkok E, Orhan N, Cakir U, Kilic G, Ozbek Z, Ince N, Kara I.

Istanbul Erenkoy Psychiatric and Neurological Disorders Hospital, Istanbul, Turkey. cemsmile@hotmail.com

BACKGROUND: Oxidative stress and free radical-induced toxicity have been implicated in the pathophysiology of schizophrenia. In this study, we examined paraoxonase (PON1)-55/192 polymorphisms and PON1 activity in patients with schizophrenia, first-degree relatives of schizophrenic patients, and healthy controls. METHODS: This study consisted of 292 healthy participants, 267 unrelated patients with schizophrenia and 311 first-degree relatives of schizophrenic patients. PON1 55 (rs 854560) and PON1 192 (rs 662) polymorphisms were performed by restriction fragment length polymorphism. RESULTS: The frequencies of the QQ and LL genotypes were significantly overpresented in controls compared with those of schizophrenic patients and their relatives. In contrast, the RR genotype was more prevalent in patients than their relatives and healthy controls. The frequencies of the LM and QR genotypes in relatives were higher than controls. Serum PON1 activities of controls were significantly higher when compared with both schizophrenic patients and their relatives. The RR and LL genotypes were associated with a significantly increased PON1 activity as compared with QR or QQ and MM or LM genotypes, respectively, in all groups. CONCLUSION: This is the first study that shows the association between PON1-55/192 polymorphisms and schizophrenia. Our data suggest that the subjects carrying R allele or RR genotype might be susceptible to schizophrenia and subjects with QQ or LL might be protected against schizophrenia. First-degree relatives of schizophrenic patients have higher heterozygote genotypes, suggesting that this group can shift either to patient or control group depending on their allele types and environmental factors. PON1 genetic variations are also associated with PON1 activities. Reduced PON1 activity in patients and their relatives might result from the combined effects of more than one polymorphic variant in PON1 or other genes and/or increased oxidative stress, supporting the hypothesis that reactive oxygen species-mediated cellular damage might contribute to the neuropathology of schizophrenia.


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