Influence of polymorphisms in genes SLC1A1, GRIN2B, and GRIK2 on clozapine-induced obsessive-compulsive symptoms
Influence of polymorphisms in genes SLC1A1, GRIN2B, and GRIK2 on clozapine-induced obsessive-compulsive symptoms
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DOI：
10.1007/s00213-013-3137-2
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发表时间：
2013-11-01
影响因子：
3.4
通讯作者：
Zhang, Chen
中科院分区：
文献类型：
--
作者：
Cai, Jun;Zhang, Wen;Zhang, Chen
临床观察表明，非典型抗精神病药物，尤其是氯氮平，可引起精神分裂症患者的强迫症。最近的神经影像和临床试验数据表明，谷氨酸神经传递的改变在强迫症(OCD)的病因中发挥了作用，SLC1A1、GRIN2B和GRIK2都被报道调节谷氨酸的传递并影响强迫症的病理生理。本研究旨在确定SLC1A1、GRIN2B和GRIK2是否与氯氮平引起的强迫症有关。采用Yale-Brown强迫量表(Y-BOCS)评定强迫症症状的严重程度。根据Y-BOCS评分，250例患者被分为OC组和非OC组(分别为有或无OC症状的患者)。此外，还发现了3个已报道的强迫症易感基因SLC1A1(Rs2228622)、GRIN2B(Rs890)和GRIK2(Rs1556995)，并观察了rs2228622A和rs890T等位基因与强迫症症状的关联趋势。采用多因素降维的方法，发现SLC1A1和GRIN2B在显著的两位点基因-基因交互作用模型中存在交互作用(p=0.0021)。进一步分析发现SLC1A1和GRIN2B在Y-BOCS得分上存在显著的交互作用(F(6,137)=7.650，p&t；0.001)，且AA/TT基因型个体的Y-BOCS得分显著高于除AG/TT以外的其他基因型。这些结果提示SLC1A1、GRIN2B以及两者之间的交互作用可能使服用氯氮平的精神分裂症患者更容易出现OC症状。
Clinical observations indicate that atypical antipsychotics, especially clozapine, induce obsessive-compulsive (OC) symptoms in schizophrenia patients. Recent data from neuroimaging and clinical trials suggest a role for altered glutamate neurotransmission in the etiology of OC disorder (OCD), and SLC1A1, GRIN2B, and GRIK2 have all been reported to regulate glutamate transmission and affect OCD pathophysiology.This study aimed to determine whether SLC1A1, GRIN2B, and GRIK2 are associated with clozapine-induced OC symptoms.A total of 250 clinically stable schizophrenia patients receiving clozapine treatment were recruited. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was used to evaluate the severity of OC symptoms. Based on their Y-BOCS scores, 250 patients were divided into the OC and non-OC groups (patients with or without OC symptoms, respectively). Additionally, three reported OCD susceptibility polymorphisms, SLC1A1 (rs2228622), GRIN2B (rs890), and GRIK2 (rs1556995), were genotyped.Trends of association with OC symptoms were observed in rs2228622A and rs890T alleles. SLC1A1 and GRIN2B interaction was found in the significant two-locus gene-gene interaction model (p = 0.0021), using the multifactor dimensionality reduction method. Further analysis showed a significant interaction between SLC1A1 and GRIN2B on the Y-BOCS score (F (6, 137) = 7.650, p < 0.001), and individuals with AA/TT genotypes had a significantly higher mean Y-BOCS score than those with other genotypes, except AG/TT.These results suggest that SLC1A1, GRIN2B, and interactions between the two may potentially confer a susceptibility to OC symptoms in schizophrenia patients receiving clozapine.