Population-based and family-based association study of 5/UTR polymorphism of the reelin gene and schizophrenia
Population-based and family-based association study of 5/UTR polymorphism of the reelin gene and schizophrenia
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DOI：
10.1002/ajmg.b.30191
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发表时间：
2005-08-05
影响因子：
2.8
通讯作者：
Krebs, MO
中科院分区：
文献类型：
--
作者：
Goldberger, C;Gourion, D;Krebs, MO
Reelin是一种糖蛋白，参与神经发育过程中增殖神经元的迁移和定位以及突触连接。它还可以调节整个生命的神经元可塑性。因此，reelin基因是精神分裂症的候选基因。我们研究了266名无血缘关系的法国白人患者、156名其父母和103名对照者中reelin基因5 '非翻译区CGG重复多态性与精神分裂症的关系。我们发现患者和对照组之间的等位基因分布没有差异，尽管对照组中基因型8 - 8的患病率显著更高（CLUMP T3：chi（2）= 6.3，P = 0.035）。在家族内分析中没有发现明显的传递不平衡。为了完善我们的表型特征，并根据趋同的证据表明，治疗阻力与异常神经发育的指数，我们研究了reelin基因多态性和抗精神病药物的反应之间的关联。抗精神病药物治疗有效的患者具有更高的（CGG）10等位基因和（CGG）（10）基因型频率（分别为P = 0.02; P = 0.006），基因型的比值比为4.2（CI =[1.4; 12.4]）。我们的研究结果弱支持reelin基因变异与精神分裂症作为一个整体的关联，但表明reelin可能与难治性精神分裂症。(c)2005 Wiley-Liss，Inc.
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: chi(2) = 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. (c) 2005 Wiley-Liss, Inc.