TITLE

Excess of transmission of the G allele of the -1438A/G polymorphism of the 5-HT2A receptor gene in patients with schizophrenia responsive to antipsychotics

AUTHOR(S)
Benmessaoud, Dalila; Hamdani, Nora; Boni, Claudette; Ramoz, Nicolas; Hamon, Michel; Kacha, Farid; Gorwood, Philip
PUB. DATE
January 2008
SOURCE
BMC Psychiatry;2008, Vol. 8, Special section p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: The -1438A/G polymorphism of the 5-HT2A gene has been found to be associated with clinical response to clozapine and other second generation antipsychotics. Testing the impact of this marker on response to first generation antipsychotics (which have a lower affinity for the 5-HT2A receptor) provides the opportunity to help disentangling the two different roles that this polymorphism might have. A psychopharmacogenetic role should be detected only for antipsychotics with high affinity to the 5-HT2A receptor (therefore to second generation antipsychotics). An alternative role would imply tagging a subgroup of patients responsive to any antipsychotic, whatever their affinity, meaning that the association is more depending on non pharmacological charaterictics, such as clinical specificities. Methods: A family-based sample of 100 Algerian patients with schizophrenia (according to DSM-IV criteria) and their 200 biological parents was recruited, in order to avoid stratification biases. Patients were all treated, or have been treated, by conventional antipsychotics (mainly haloperidol) for at least four weeks, at appropriate dosage. May and Dencker scale was used to distinguish responders and non responders. Results: No allele of the -1438A/G polymorphism of the 5-HT2A gene was transmitted in excess (50 transmitted for 38 untransmitted) in the whole sample of patients with schizophrenia (p = .90). In contrast, a significant excess of transmission of the G allele was observed (p = .02) in the subgroup of patients with good treatment response (17 transmitted for 6 untransmitted). Conclusion: Using a TDT approach, we showed that the G allele of the -1438A/G polymorphism of the gene coding for the 5-HT2A receptor was associated to schizophrenia with good response to conventional antipsychotics, although this conclusion is based on 88 informative patients only. Because previous data showed the same result with atypical antipsychotics, it can be concluded that the G allele tags a subgroup of schizophrenic patients with greater chance of improvement with antipsychotics of either type.
ACCESSION #
35702796

 

Related Articles

  • Association between the brain-derived neurotrophic factor Val66Met polymorphism and therapeutic response to olanzapine in schizophrenia patients. Nikolac Perkovic, Matea; Nedic Erjavec, Gordana; Zivkovic, Maja; Sagud, Marina; Uzun, Suzana; Mihaljevic-Peles, Alma; Kozumplik, Oliver; Muck-Seler, Dorotea; Pivac, Nela // Psychopharmacology;Sep2014, Vol. 231 Issue 18, p3757 

    Rationale: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a major role in neurogenesis and neuroplasticity, and in the modulation of several neurotransmitter systems including the dopaminergic system. There are mixed reports about the association between the BDNF Val66Met...

  • Association of Disrupted in Schizophrenia 1 (DISC1) missense variants with ultra-resistant schizophrenia. Mouaffak, F; Kebir, O; Chayet, M; Tordjman, S; Vacheron, M N; Millet, B; Jaafari, N; Bellon, A; Olié, J P; Krebs, M-O // Pharmacogenomics Journal;Aug2011, Vol. 11 Issue 4, p267 

    Three common missense variants of the Disrupted in Schizophrenia 1 (DISC1) gene, rs3738401 (Q264R), rs6675281 (L607F) and rs821616 (S704C), have been variably associated with the risk of schizophrenia. In a case-control study, we examine whether these gene variants are associated with...

  • The dopamine D3 receptor (DRD3) Ser9Gly polymorphism and schizophrenia: a haplotype relative risk study and association with clozapine response. Malhotra, A.K.; Goldman, D.; Buchanan, R.W.; Rooney, W.; Clifton, A.; Kosmidis, M.H.; Breier, A.; Pickar, D. // Molecular Psychiatry;1998, Vol. 3 Issue 1, p72 

    Several lines of evidence suggest that the dopamine D[sub 3] receptor is involved in the pathophysiology of schizophrenia. The D[sub 3] receptor gene (DRD3) contains a polymorphism resulting in a serine-glycine substitution in the N-terminus of the receptor. Shaikh and colleagues have reported a...

  • Effect of Serotonin-Related Gene Polymorphisms on Pathogenesis and Treatment Response in Korean Schizophrenic Patients. Yong-Ku Kim; Ho-Kyoung Yoon // Behavior Genetics;Sep2011, Vol. 41 Issue 5, p709 

    Serotonin has been implicated in the pathophysiology of several psychiatric disorders including schizophrenia. Serotonergic system-related genes may be good candidates in investigating the genetic basis of schizophrenia. We aimed to investigate the associations of HTR1A C-1019G, HTR2A-1438A/G,...

  • Gene-gene interactions of the INSIG1 and INSIG2 in metabolic syndrome in schizophrenic patients treated with atypical antipsychotics. Liou, Y-J; Bai, Y M; Lin, E; Chen, J-Y; Chen, T-T; Hong, C-J; Tsai, S-J // Pharmacogenomics Journal;Feb2012, Vol. 12 Issue 1, p54 

    The use of atypical antipsychotics (AAPs) is associated with increasing the risk of the metabolic syndrome (MetS), which is an important risk factor for cardiovascular disease and diabetes. Two insulin-induced gene (INSIG) isoforms, designated INSIG-1 and INSIG-2 encode two proteins that mediate...

  • Association study of 12 polymorphisms spanning the dopamine D2 receptor gene and clozapine treatment response in two treatment refractory/intolerant populations. Hwang, Rudi; Shinkai, Takahiro; De Luca, Vincenzo; Müller, Daniel J.; Xingqun Ni; Macciardi, Fabio; Potkin, Steven; Lieberman, Jeffrey A.; Meltzer, Herbert Y.; Kennedy, James L. // Psychopharmacology;Aug2005, Vol. 181 Issue 1, p179 

    Dopamine D2 receptor blockade is the major basis for the antipsychotic action of typical antipsychotic drugs (AP) and a necessary but not sufficient basis for the antipsychotic action of atypical APs such as clozapine and other multireceptor antagonists which rely, in part, upon 5-HT2A...

  • CYP1A2*1F Polymorphism Decreases Clinical Response to Clozapine in Patients with Schizophrenia. Balibey, Hakan; Basoglu, Cengiz; Lundgren, Stefan; Babaoglu, Melih O.; Yasar, Umit; Herken, Hasan; Rane, Anders; Bozkurt, Atilla; Cetin, Mesut // Klinik Psikofarmakoloji Bulteni;Jun2011, Vol. 21 Issue 2, p93 

    Introduction: Genetic polymorphisms of cytochrome P450 (CYP) may predict the treatment response or occurrence of side effects of antipsychotic drugs. Aim: We studied the association of response to clozapine treatment in schizophrenic patients in relation to polymorphisms in the CYP1A2 gene....

  • ADRA1A gene is associated with BMI in chronic schizophrenia patients exposed to antipsychotics. Liu, Y.-R.; Loh, E.-W.; Lan, T.-H.; Chen, S.-F.; Yu, Y.-H.; Chang, Y.-H.; Huang, C.-J.; Hu, T.-M.; Lin, K.-M.; Yao, Y.-T.; Chiu, H.-J. // Pharmacogenomics Journal;Feb2010, Vol. 10 Issue 1, p30 

    Noradrenaline and adrenaline are neurotransmitters of the sympathetic nervous system that interact with various adrenergic receptor (ADR) subtypes, and this regulates the basal metabolic rate, thermogenesis and efficiency of energy utilization. We examined a possible role of the gene coding for...

  • OUT OF THE SHADOWS. Wilson, Clare // New Scientist;2/8/2014, Vol. 221 Issue 2955, p32 

    The article discusses alternative treatments for the psychological disorder schizophrenia that do not involve drugs. Topics include schizophrenic Peter Bullimore, who experienced debilitating side effects from his medicine, how he brought his schizophrenia under control through group therapy,...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics