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台湾汉族人群中钙激活钾通道(KCNN3)基因多态性CAG重复序列与精神分裂症的遗传关联研究。

Genetic association study of a polymorphic CAG repeats array of calcium-activated potassium channel (KCNN3) gene and schizophrenia among the Chinese population from Taiwan.

作者信息

Tsai M T, Shaw C K, Hsiao K J, Chen C H

机构信息

Department of Psychiatry, Tzu-Chi General Hospital, Hualien City, Taiwan.

出版信息

Mol Psychiatry. 1999 May;4(3):271-3. doi: 10.1038/sj.mp.4000482.

Abstract

Chandy et al suggested that a novel human neuronal small conductance, calcium-activated potassium channel gene, KCNN3, might be a candidate for schizophrenia. The KCNN3 cDNA sequences contain two stretches of CAG trinucleotide repeats encoding two separate polyglutamine segments near the N-terminus of this channel protein. The second CAG repeat was found to be highly polymorphic in the Caucasian population from both Europe and USA. Upon comparing the allelic frequency distribution between schizophrenic patients and ethnically matched controls, a significant excess of longer CAG repeats in schizophrenic patients was observed. A similar result was obtained in a recent replication study by Bowen et al, performed in Caucasians from UK or Eire. These results suggest an association between the longer CAG repeat allele of the KCNN3 gene and schizophrenia susceptibility. To verify if similar results can be observed in the Chinese population, we carried out a case-control study to compare the allelic frequency distribution of the CAG repeat of the KCNN3 gene between 92 Chinese schizophrenic patients and 100 normal controls from Taiwan. No significant difference of the allelic frequency distribution of the second CAG repeats was detected between the two groups (Wilcoxon Rank Sum test, P = 0.664). In addition, no over-representation of CAG repeats longer than the mode (19 repeats) was found in the patients' group (Fisher's exact test, P = 0.739). Thus, our data do not support that the second polymorphic CAG repeat of the KCNN3 gene may have an association with schizophrenia in our population.

摘要

钱迪等人提出,一种新的人类神经元小电导钙激活钾通道基因KCNN3可能是精神分裂症的候选基因。KCNN3的cDNA序列包含两段CAG三核苷酸重复序列,在该通道蛋白的N端附近编码两个独立的聚谷氨酰胺片段。发现第二个CAG重复序列在欧洲和美国的白种人群中具有高度多态性。在比较精神分裂症患者与种族匹配的对照组之间的等位基因频率分布时,观察到精神分裂症患者中较长CAG重复序列明显过多。鲍文等人最近在来自英国或爱尔兰的白种人中进行的一项重复研究也得到了类似结果。这些结果表明,KCNN3基因较长的CAG重复等位基因与精神分裂症易感性之间存在关联。为了验证在中国人群中是否能观察到类似结果,我们进行了一项病例对照研究,比较了92名中国台湾精神分裂症患者和100名正常对照者之间KCNN3基因CAG重复序列的等位基因频率分布。两组之间未检测到第二个CAG重复序列的等位基因频率分布有显著差异(Wilcoxon秩和检验,P = 0.664)。此外,在患者组中未发现CAG重复序列超过众数(19次重复)的过度表现(Fisher精确检验,P = 0.739)。因此,我们的数据不支持KCNN3基因的第二个多态性CAG重复序列可能与我们人群中的精神分裂症有关联这一观点。

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