A study of the effects of chromogranin B gene polymorphisms on the pathophysiology of various psychiatic disorders

我们在以前的工作中发现精神分裂症和染色体20p12.3上的D20 S95之间存在显著关联。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D20 S95侧翼的D20 S882和D20 S905相关。嗜铬粒蛋白B基因（CHGB）距离D20 S905约30 kb。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元细胞的酸性分泌蛋白，其在慢性精神分裂症患者脑脊液（CSF）中的水平降低。我们在24例日本精神分裂症患者中用PCR直接测序方法筛选CHGB的多态性，共鉴定出22个多态性。检测到的多态性的等位基因和基因型分布进行了比较无关的日本精神分裂症患者（n=192）和健康对照组（n=192）。1058 C/G（A353 G）和1104 A/G（E368 E）等位基因分布在精神分裂症患者和对照组之间存在统计学显著差异。1058 C/G和1104 A/G等位基因几乎完全连锁不平衡，与D20 S95连锁不平衡。结果表明，CHGB变异参与了精神分裂症的易感性在我们的研究人群。

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(CSF) levels has been reported to decrease in patients with chronic schizophrenia. We screened for polymorphisms in CHGB with PCR 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 controls (n=192). Statistically significant differences in the allelic distributions were found between schizophrenic patients and controls for 1058C/G (A353G) and 1104A/G (E368E). The 1058C/G and 1104A/G alleles were in almost complete linkage disequilibrium and were in linkage disequilibrium with D20S95. Results suggest that the CHGB variations are involved in the susceptibility to schizophrenia in our study population.