The DTNBP1 (dysbindin) gene contributes to schizophrenia, depending on family history of the disease.
The DTNBP1 (dysbindin) gene contributes to schizophrenia, depending on family history of the disease.
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DOI：
10.1086/379928
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发表时间：
2003-12
影响因子：
9.8
通讯作者：
A. van den Bogaert;J. Schumacher;T. Schulze;Andreas C. J. Otte;S. Ohlraun;S. Kovalenko;T. Becker;J. Freudenberg;E. Jönsson;M. Mattila‐Evenden;G. Sedvall;P. Czerski;P. Kapelski;J. Hauser;W. Maier;M. Rietschel;P. Propping;M. Nöthen;S. Cichon
中科院分区：
文献类型：
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作者：
A. van den Bogaert;J. Schumacher;T. Schulze;Andreas C. J. Otte;S. Ohlraun;S. Kovalenko;T. Becker;J. Freudenberg;E. Jönsson;M. Mattila‐Evenden;G. Sedvall;P. Czerski;P. Kapelski;J. Hauser;W. Maier;M. Rietschel;P. Propping;M. Nöthen;S. Cichon
我们在三个精神分裂症受试者和德国(418例，285名对照)、波兰(294例，113名对照)和瑞典(142例，272名对照)血统的未受影响的对照组受试者的三个样本中，研究了营养不良蛋白结合蛋白1(DTNBP1)的基因，或称dybindin，它被强烈建议为精神分裂症的位置候选基因。我们分析了五个单核苷酸多态(P1635、P第1325、P1320、P1757和P1578)，并在瑞典样本中发现了显著的关联证据，而在德国或波兰的样本中则没有。瑞典样本中的结果在对那些有精神分裂症阳性家族史的病例进行单独分析后变得更加重要，在这些病例中，五种标记单倍型A-C-A-T-T的P值为0.00009(对照组为3.1%，病例为17.8%；OR为6.75；经Bonferroni校正后，P=.00153)。我们的结果表明，在有家族疾病负担的病例中，dybindin基因的遗传变异特别涉及精神分裂症的发展。这也解释了在连续确定的病例对照样本中复制这种关联的困难，这些样本通常只包括一小部分有家族病史的受试者。
We have investigated the gene for dystrobrevin-binding protein 1 (DTNBP1), or dysbindin, which has been strongly suggested as a positional candidate gene for schizophrenia, in three samples of subjects with schizophrenia and unaffected control subjects of German (418 cases, 285 controls), Polish (294 cases, 113 controls), and Swedish (142 cases, 272 controls) descent. We analyzed five single-nucleotide polymorphisms (P1635, P1325, P1320, P1757, and P1578) and identified significant evidence of association in the Swedish sample but not in those from Germany or Poland. The results in the Swedish sample became even more significant after a separate analysis of those cases with a positive family history of schizophrenia, in whom the five-marker haplotype A-C-A-T-T showed a P value of.00009 (3.1% in controls, 17.8% in cases; OR 6.75; P=.00153 after Bonferroni correction). Our results suggest that genetic variation in the dysbindin gene is particularly involved in the development of schizophrenia in cases with a familial loading of the disease. This would also explain the difficulty of replicating this association in consecutively ascertained case-control samples, which usually comprise only a small proportion of subjects with a family history of disease.