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多巴胺β羟化酶基因与注意缺陷多动障碍合并破坏性行为障碍之间的关联

[Association between dopamine beta hydroxylase gene and attention deficit hyperactivity disorder complicated with disruptive behavior disorder].

作者信息

Zhang Hao-Bo, Wang Yu-Feng, Li Jun, Wang Bing, Yang Li

机构信息

Child Psychiatric Unit, Institute of Mental Health, Peking University, Beijing 100083, China.

出版信息

Zhonghua Er Ke Za Zhi. 2005 Jan;43(1):26-30.

Abstract

OBJECTIVE

Attention deficit hyperactivity disorder (ADHD), a common behavior disorder of childhood, is a highly heterogeneous disease frequently accompanied by various mental disorders, including disruptive behavior disorder (DBD). Studies show that children suffering from ADHD with DBD are at higher risk of antisocial personality, substance abuse, and social adaptations disorder at their adulthood. The dopamine beta hydroxylase (DbetaH) is the key enzyme to ADHD since it catalyzes the conversion of dopamine to norepinephrine, and dysfunction there of is believed to be one of the causes of the disorder. To explore the association between DBH gene and ADHD complicated with or without DBD, the authors analyzed the transmission of a novel polymorphism DBH -1021C-->T, which is found associated with plasma DbetaH activity, in ADHD nuclear families using transmission disequilibrium test (TDT).

METHODS

Consensus diagnoses were based on the DSM-IV. The samples included those from 292 Chinese Han nuclear families with ADHD probands. Genotypes of DBH -1021C-->T polymorphism were determined by PCR amplification, endonuclease digesting and electrophoresis. The transmission of DBH -1021C-->T polymorphism in ADHD nuclear families with or without DBD was analyzed by TDT.

RESULTS

The results showed that there was transmission disequilibrium between DBH-1021C-->T polymorphism and ADHD with or without DBD. In ADHD comorbid with DBD, T allele was preferentially transmitted (P < 0.05); and in ADHD without DBD, so was the C allele (P < 0.05). Among the three subtypes of ADHD, only ADHD-C subtype with DBD had an increased transmission of T allele (P < 0.05).

CONCLUSION

There is an association between DBH gene and ADHD comorbid with or without DBD, but the preferential transmission alleles are different. The low activity T allele is increased to transmit in ADHD with DBD, while the high activity C allele is preferentially transmitted in ADHD without DBD. The results support the proposition that the genetic mechanism is different between ADHD comorbid with or without DBD. We also found that only ADHD-C subtype with DBD is associated with DBH -1021C-->T polymorphism in three subtypes of ADHD, which may suggest that there is a more intense relationship between DBD and ADHD-C subtype.

摘要

目的

注意缺陷多动障碍(ADHD)是一种常见的儿童行为障碍,是一种高度异质性疾病,常伴有各种精神障碍,包括破坏性行为障碍(DBD)。研究表明,患有ADHD合并DBD的儿童在成年后患反社会人格、药物滥用和社会适应障碍的风险更高。多巴胺β羟化酶(DbetaH)是ADHD的关键酶,因为它催化多巴胺转化为去甲肾上腺素,其功能障碍被认为是该疾病的病因之一。为了探讨DBH基因与合并或不合并DBD的ADHD之间的关联,作者使用传递不平衡检验(TDT)分析了一种新的多态性DBH -1021C→T在ADHD核心家庭中的传递情况,该多态性与血浆DbetaH活性相关。

方法

共识诊断基于《精神疾病诊断与统计手册》第四版(DSM-IV)。样本包括来自292个有ADHD先证者的中国汉族核心家庭。通过PCR扩增、内切酶消化和电泳确定DBH -1021C→T多态性的基因型。使用TDT分析DBH -1021C→T多态性在合并或不合并DBD的ADHD核心家庭中的传递情况。

结果

结果表明,DBH-1021C→T多态性与合并或不合并DBD的ADHD之间存在传递不平衡。在合并DBD的ADHD中,T等位基因优先传递(P < 0.05);在不合并DBD的ADHD中,C等位基因也是如此(P < 0.05)。在ADHD的三个亚型中,只有合并DBD的ADHD-C亚型T等位基因传递增加(P < 0.05)。

结论

DBH基因与合并或不合并DBD的ADHD之间存在关联,但优先传递的等位基因不同。低活性的T等位基因在合并DBD的ADHD中传递增加,而高活性的C等位基因在不合并DBD的ADHD中优先传递。结果支持合并或不合并DBD的ADHD之间遗传机制不同的观点。我们还发现,在ADHD的三个亚型中,只有合并DBD的ADHD-C亚型与DBH -1021C→T多态性相关,这可能表明DBD与ADHD-C亚型之间存在更密切的关系。

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