Association study of polymorphisms in the neutral amino acid transporter genes SLC1A4, SLC1A5 and the glycine transporter genes SLC6A5, SLC6A9 with schizophrenia.
Association study of polymorphisms in the neutral amino acid transporter genes SLC1A4, SLC1A5 and the glycine transporter genes SLC6A5, SLC6A9 with schizophrenia.
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中性氨基酸转运蛋白基因SLC1A4，SLC1A5和甘氨酸转运蛋白基因SLC6A5，SLC6A9，具有精神分裂症的结合研究。
DOI：
10.1186/1471-244x-8-58
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发表时间：
2008-07-18
期刊：
影响因子：
4.4
通讯作者：
Fukumaki Y
中科院分区：
文献类型：
--
作者：
Deng X;Sagata N;Takeuchi N;Tanaka M;Ninomiya H;Iwata N;Ozaki N;Shibata H;Fukumaki Y
基于精神分裂症发病机制的代谢能功能障碍假说，我们一直在进行精神分裂症与代谢能传递相关基因的系统关联研究。我们在此报告了分别编码中性氨基酸转运体ASCT 1、ASCT 2的SLC 1A 4、SLC 1A 5和编码甘氨酸转运体GLYT 2、GLYT 1的SLC 6A 5、SLC 6A 9与精神分裂症的相关性研究。我们最初使用100例日本病例对照对检测了分布在4个基因区域的21个单核苷酸多态性（SNP）与精神分裂症的关联，并检查了等位基因、基因型和单体型与精神分裂症的关联。在全尺寸样本（400例病例和420例对照）中检查观察到的标称显著性。我们观察到SLC 1A 4的SNP 2（P = 0.021）和SNP 3（P = 0.029）、SLC 6A 5的SNP 1（P = 0.009）和SNP 2（P = 0.022）与精神分裂症名义上显著的单标记关联。我们还观察到在SLC 1A 4的SNP 2-SNP 7（P = 0.037）和SLC 6A 5的SNP 1-SNP 4（P = 0.043）的组合中与精神分裂症的名义上显著的单倍型关联。我们检查了全尺寸样本集中的所有标称显著性，除了一个LD不足的单倍型。SLC 6A 5的SNP 1与精神分裂症的关联在全样本集中得到证实（P = 0.018）。我们的结论是，至少有一个精神分裂症的易感基因可能位于或附近的SLC 6A 5，而SLC 1A 4，SLC 1A 5和SLC 6A 9不太可能是精神分裂症的主要易感基因在日本人口。
Based on the glutamatergic dysfunction hypothesis for schizophrenia pathogenesis, we have been performing systematic association studies of schizophrenia with the genes involved in glutametergic transmission. We report here association studies of schizophrenia with SLC1A4, SLC1A5 encoding neutral amino acid transporters ASCT1, ASCT2, and SLC6A5, SLC6A9 encoding glycine transporters GLYT2, GLYT1, respectively. We initially tested the association of 21 single nucleotide polymorphisms (SNPs) distributed in the four gene regions with schizophrenia using 100 Japanese cases-control pairs and examined allele, genotype and haplotype association with schizophrenia. The observed nominal significance were examined in the full-size samples (400 cases and 420 controls). We observed nominally significant single-marker associations with schizophrenia in SNP2 (P = 0.021) and SNP3 (P = 0.029) of SLC1A4, SNP1 (P = 0.009) and SNP2 (P = 0.022) of SLC6A5. We also observed nominally significant haplotype associations with schizophrenia in the combinations of SNP2-SNP7 (P = 0.037) of SLC1A4 and SNP1-SNP4 (P = 0.043) of SLC6A5. We examined all of the nominal significance in the Full-size Sample Set, except one haplotype with insufficient LD. The significant association of SNP1 of SLC6A5 with schizophrenia was confirmed in the Full-size Sample Set (P = 0.018). We concluded that at least one susceptibility locus for schizophrenia may be located within or nearby SLC6A5, whereas SLC1A4, SLC1A5 and SLC6A9 are unlikely to be major susceptibility genes for schizophrenia in the Japanese population.