日本精神分裂症患者5号染色体GABAA受体簇的关联分析。

Association analysis of chromosome 5 GABAA receptor cluster in Japanese schizophrenia patients.

作者信息

Ikeda Masashi, Iwata Nakao, Suzuki Tatsuyo, Kitajima Tsuyoshi, Yamanouchi Yoshio, Kinoshita Yoko, Inada Toshiya, Ujike Hiroshi, Ozaki Norio

机构信息

Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.

出版信息

Biol Psychiatry. 2005 Sep 15;58(6):440-5. doi: 10.1016/j.biopsych.2005.05.002. Epub 2005 Jul 5.

DOI:10.1016/j.biopsych.2005.05.002

PMID:15993854

Abstract

BACKGROUND

Several investigations suggest that abnormalities in gamma-amino butyric acid (GABA) neurotransmission systems may be related to the pathophysiology of schizophrenia. A GABA(A) receptor gene cluster on 5q31-35 (beta2 [GABRB2], alpha6 [GABRA6], alpha1 [GABRA1], and gamma2 [GABRG2] subunit genes) is one of the most attractive candidate regions for schizophrenia susceptibility.

METHODS

We performed 1) systematic polymorphism search of GABRB2, GABRA6, and GABRA1, in addition to our colleague's study of GABRG2; 2) evaluation of linkage disequilibrium (LD) within this cluster with 35 single nucleotide polymorphisms (SNPs); 3) "selection of haplotype-tagging (ht) SNPs"; and 4) two-stage association analysis that comprised first-set screening analysis of all htSNPs (288 Japanese schizophrenia patients and 288 control subjects) and second-set replication analysis of the positive htSNPs (901 schizophrenic patients and 806 control subjects).

RESULTS

In the first-set scan, we found a significant association of two htSNPs in GABRA1, but no association of GABRB2, GABRA6, and GABRG2. In the following second-set analysis, however, we could not confirm these significant associations.

CONCLUSIONS

These results indicate that this gene cluster may not play a major role in Japanese schizophrenia. They also raised an alert with regard to preliminary genetic association analysis using a small sample size.

摘要

背景

多项研究表明，γ-氨基丁酸（GABA）神经传递系统异常可能与精神分裂症的病理生理学相关。位于5q31 - 35的GABA(A)受体基因簇（β2 [GABRB2]、α6 [GABRA6]、α1 [GABRA1]和γ2 [GABRG2]亚基基因）是精神分裂症易感性最具吸引力的候选区域之一。

方法

我们进行了以下研究：1）除了同事对GABRG2的研究外，对GABRB2、GABRA6和GABRA1进行系统的多态性搜索；2）利用35个单核苷酸多态性（SNP）评估该基因簇内的连锁不平衡（LD）；3）“选择单倍型标签（ht）SNP”；4）两阶段关联分析，第一阶段对所有htSNP进行筛选分析（288名日本精神分裂症患者和288名对照受试者），第二阶段对阳性htSNP进行重复分析（901名精神分裂症患者和806名对照受试者）。