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Population-based and family-based association study of 5′UTR polymorphism of the reelin gene and schizophrenia

Authors

  • Céline Goldberger,

    1. INSERM E117; Université de Paris 5; CH Sainte-Anne, 2ter rue d'Alesia, Paris, France
    2. Service Hospitalo Universitaire, CH Sainte Anne, 7 rue Cabanis, Paris, France
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  • David Gourion,

    1. INSERM E117; Université de Paris 5; CH Sainte-Anne, 2ter rue d'Alesia, Paris, France
    2. Service Hospitalo Universitaire, CH Sainte Anne, 7 rue Cabanis, Paris, France
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  • Sophie Leroy,

    1. INSERM E117; Université de Paris 5; CH Sainte-Anne, 2ter rue d'Alesia, Paris, France
    2. Service Hospitalo Universitaire, CH Sainte Anne, 7 rue Cabanis, Paris, France
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  • Franck Schürhoff,

    1. Service de psychiatrie adulte, Hôpital Albert Chenevier et Henri Mondor, 40 rue Mesly, Créteil, France
    2. Unité INSERM U513, 40 rue Mesly, Créteil, France
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  • Marie-Chantal Bourdel,

    1. INSERM E117; Université de Paris 5; CH Sainte-Anne, 2ter rue d'Alesia, Paris, France
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  • Marion Leboyer,

    1. Service de psychiatrie adulte, Hôpital Albert Chenevier et Henri Mondor, 40 rue Mesly, Créteil, France
    2. Unité INSERM U513, 40 rue Mesly, Créteil, France
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  • Marie-Odile Krebs

    Corresponding author
    1. INSERM E117; Université de Paris 5; CH Sainte-Anne, 2ter rue d'Alesia, Paris, France
    2. Service Hospitalo Universitaire, CH Sainte Anne, 7 rue Cabanis, Paris, France
    • Inserm E117 Service Hospitalo-Universitaire, CH Sainte-Anne, 7 rue Cabanis, 75014 Paris, France.
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Abstract

Reelin is a glycoprotein involved in the migration and positioning of proliferating neurons and synaptic connectivity during neurodevelopment. It may also modulate neuronal plasticity throughout life. Therefore, the reelin gene is a candidate gene for schizophrenia. We examined the association of the CGG repeat polymorphism in the 5′-untranslated region of the reelin gene with schizophrenia in 266 unrelated French Caucasian patients, 156 of their parents, and 103 controls. We found no difference in the allele distribution between patients and controls although there was a significant higher prevalence of the genotype 8-8 in controls (CLUMP T3: χ2 = 6.3, P = 0.035). There was no significant transmission disequilibrium in intrafamilial analysis. To refine our phenotypic characterization and in accordance with converging evidence suggesting that treatment resistance is associated with indices of abnormal neurodevelopment, we studied the association between reelin gene polymorphism and response to antipsychotics. Patients who responded to antipsychotics had a higher frequency of both the (CGG)10 allele and (CGG)10-containing genotypes (P = 0.02; P = 0.006, respectively), with an odd ratio for genotypes of 4.2 (CI = [1.4;12.4]). Our results weakly support an association of reelin gene variants with schizophrenia as a whole, yet suggest that reelin could be associated with treatment-resistant schizophrenia. © 2005 Wiley-Liss, Inc.

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