Failure to Confirm Genetic Association of the CHI3L1 Gene With Schizophrenia in Japanese and Chinese Populations
Failure to Confirm Genetic Association of the CHI3L1 Gene With Schizophrenia in Japanese and Chinese Populations
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DOI：
10.1002/ajmg.b.30847
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发表时间：
2009-06-05
影响因子：
2.8
通讯作者：
Yoshikawa, Takeo
中科院分区：
文献类型：
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作者：
Yamada, Kazuo;Hattori, Eiji;Yoshikawa, Takeo
最近，几丁质酶3-Like 1（CHI3L1）基因启动子区的三个常见多态性rs6691378、rs10399805和rs4950928被鉴定为中国汉族人群中的精神分裂症易感单核苷酸多态性（SNP）。包含这些 SNP 的高危单倍型也与外周血细胞中 CHI3L1 表达降低有关。相比之下，两项独立的死后大脑研究报告称，精神分裂症患者的海马体和前额皮质中的转录物表达升高。该基因编码一种分泌糖蛋白（HC-gp39 或 YKL40），被认为参与炎症过程。这些证据表明 CHI3L1 在精神分裂症发病机制中的潜在重要性。在这项研究中，我们的目的是使用两个样本集来复制先前的遗传关联发现，一组是与原始报告中使用的种族相同的中国样本（293个家谱，由1,163名受试者组成），第二组来自相对接近的日本人群（570名精神分裂症患者和570名匹配对照）。我们分析了与原始研究中相同的五个 SNP，包括三个启动子 SNP。在我们的样本集中，这些 SNP 均未显示出与精神分裂症的关联信号（P 值 >0.108）。这些结果表明，CHI3L1 对精神分裂症的遗传贡献是可变的，尽管它在机制上参与了疾病过程。 (C) 2008 Wiley-Liss, Inc.
Recently, three common polymorphisms in the promoter region of the Chitinase 3-Like 1 (CHI3L1) gene, rs6691378, rs10399805 and rs4950928, have been identified as schizophrenia predisposing single nucleotide polymorphisms (SNPs) in the Han Chinese population. The at-risk haplotype comprising these SNPs was also related to decreased expression of CHI3L1 in peripheral blood cells. In contrast, two independent postmortem brain studies have reported elevated expression of the transcript in the hippocampus and prefrontal cortex, from schizophrenic patients. The gene encodes a secreted glycoprotein (HC-gp39 or YKL40), which is deemed to be involved in the inflammatory process. These pieces of evidence signify the potential importance of CHI3L1 in the pathogenesis of schizophrenia. In this study, we aimed to replicate the prior genetic association findings using two sample sets, one set of Chinese samples (293 pedigrees consisting of 1,163 subjects) that are ethnically identical to those used in the original report and a second set from the relatively close Japanese population (570 schizophrenic patients and 570 matched controls). We analyzed the same five SNPs as in the original study, including the three promoter SNPs. None of these SNPs showed association signals with schizophrenia (P values >0.108) in our sample sets. These results suggest that the genetic contribution of CHI3L1 to schizophrenia is variable, even though it is mechanistically involved in the disease process. (C) 2008 Wiley-Liss, Inc.