Association between chromogranin B gene polymorphisms and schizophrenia in the Japanese population

Association between chromogranin B gene polymorphisms and schizophrenia in the Japanese population
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DOI:
10.1016/j.biopsych.2004.03.012
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发表时间:
2004-07-01
影响因子:
10.6
通讯作者:
Arinami, T
Arinami, T
中科院分区:
医学1区
文献类型:
--
作者:
Iijima, Y;Inada, T;Arinami, T

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背景:我们在之前的工作中发现精神分裂症与染色体20p12.3上的D20S95有显著关联。在这项研究中,我们分析了10个微卫星标记,发现精神分裂症与D20S882和D20S905的关联,这些标记位于D20S95旁边。染色体粒蛋白B基因(CHGB)来自D20S905,全长30kb。嗜铬粒蛋白B (secretogranin I)是一系列广泛表达于内分泌细胞和神经细胞的酸性分泌蛋白,有报道慢性精神分裂症患者脑脊液中嗜铬粒蛋白B水平降低。方法:采用聚合酶链反应直接测序法对24例日本精神分裂症患者的CHGB基因进行多态性筛选,共鉴定出22个多态性。比较无血缘关系的日本精神分裂症患者(n = 192)和健康对照(n = 192)之间检测到的多态性的等位基因和基因型分布。结果:精神分裂症患者与对照组1058C/G (A353G)(校正p = 7.7 × 10(-5))、1104A/G (E368E)(校正p = 8.1 × 10(-6))等位基因分布差异有统计学意义。1058C/G和1104A/G等位基因几乎处于完全连锁不平衡状态,与D20S95也处于连锁不平衡状态。结论:结果表明CHGB变异与我们研究人群对精神分裂症的易感性有关。
Background: We found in previous work a significant association between schizophrenia and D20S95 on chromosome 20p12.3. In this study, we analyzed 10 microsatellite markers and found an association of schizophrenia with D20S882 and D20S905 that flank D20S95. The chromogranin B gene (CHGB) is 30 kb from D20S905. The chromogranin B (secretogranin I) belongs to a series of acidic secretory proteins that are widely expressed in endocrine and neuronal cells, and its cerebrospinal fluid levels have been reported to decrease inpatients with chronic schizophrenia.Methods: We screened for polymorphisms in CHGB with polymerase chain reaction direct sequencing methods in 24 Japanese schizophrenic patients and identified a total of 22 polymorphisms. Allelic and genotypic distributions of detected polymorphisms were compared between unrelated Japanese schizophrenic patients (n = 192) and healthy control subjects (n = 192).Results: Statistically significant differences in the allelic distributions were found between schizophrenic patients and control subjects for 1058C/G (A353G) (corrected p = 7.7 x 10(-5)) and 1104A/G (E368E) (corrected p = 8.1 x 10(-6)). The 1058C/G and 1104A/G alleles were in almost complete linkage disequilibrium and were in linkage disequilibrium with D20S95.Conclusions: Results suggest that the CHGB variations are involved in the susceptibility to schizophrenia in our study population.