Association study of polymorphisms in the group III metabotropic glutamate receptor genes, GRM4 and GRM7, with schizophrenia
Association study of polymorphisms in the group III metabotropic glutamate receptor genes, GRM4 and GRM7, with schizophrenia
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DOI：
10.1016/j.psychres.2007.12.002
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发表时间：
2009-05
影响因子：
11.3
通讯作者：
H. Shibata;Ayako Tani;Tomoyuki Chikuhara;Rumiko Kikuta;M. Sakai;H. Ninomiya;N. Tashiro;N. Iwata-N.-Iwa
中科院分区：
文献类型：
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作者：
H. Shibata;Ayako Tani;Tomoyuki Chikuhara;Rumiko Kikuta;M. Sakai;H. Ninomiya;N. Tashiro;N. Iwata-N.-Iwa
基于谷氨酸能功能障碍参与精神分裂症病理生理的假设，我们一直在对谷氨酸受体基因与精神分裂症之间的关联进行系统的研究。在这里，我们报告的关联研究精神分裂症与第三组代谢型谷氨酸受体基因，GRM4和GRM7的多态性。我们分别在GRM4（>111 kb）和GRM7（>900 kb）的整个基因区域中选择了8个和43个常见的SNPs。我们使用100对日本人的病例对照对来扫描与精神分裂症的显著关联。我们在GRM7中发现了两个相邻的SNPs（rs12491620和rs1450099），这两个SNPs显示出与FDR校正后幸存的精神分裂症高度显著的单倍型关联。然后，我们使用扩展的样本集（404例病例和420例对照）对这两个SNP进行了额外的分型，并证实了与疾病的显著相关性。我们的结论是，精神分裂症的易感基因至少有一个位于GRM7内或附近，而GRM4是不太可能是一个主要的易感基因，精神分裂症在日本人口。
Based on the hypothesis that a glutamatergic dysfunction is involved in the pathophysiology of schizophrenia, we have been conducting systematic studies on the association between glutamate receptor genes and schizophrenia. Here we report association studies of schizophrenia with polymorphisms in group III metabotropic glutamate receptor genes, GRM4 and GRM7. We selected 8 and 43 common SNPs distributed in the entire gene regions of GRM4 (>111 kb) and GRM7 (>900 kb), respectively. We scanned significant associations with schizophrenia using 100 case-control pairs of Japanese. We identified two neighboring SNPs (rs12491620 and rs1450099) in GRM7 showing highly significant haplotype association with schizophrenia surviving the FDR correction. We then performed additional typing of the two SNPs using the expanded sample set (404 cases and 420 controls) and confirmed the significant association with the disease. We conclude that at least one susceptibility locus for schizophrenia is located within or nearby GRM7, whereas GRM4 is unlikely to be a major susceptibility gene for schizophrenia in the Japanese population.