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多巴胺β羟化酶基因多态性分析：与印度儿童注意力缺陷多动障碍的关联

Analysis of polymorphisms in the dopamine beta hydroxylase gene: association with attention deficit hyperactivity disorder in Indian children.

作者信息

Bhaduri Nipa, Sinha Swagata, Chattopadhyay Anindita, Gangopadhyay Prasanta Kumar, Singh Manoranjan, Mukhopadhyay Kanchan Kumar

机构信息

Manovikas Biomedical Research and Diagnostic Center, Kolkata 700 107, India.

出版信息

Indian Pediatr. 2005 Feb;42(2):123-9.

PMID:15767706
Abstract

OBJECTIVE

To study the association of Attention Deficit Hyperactivity Disorder (ADHD) and polymorphism in the dopamine beta hydroxylase (DBH) gene in Indian ADHD cases.

SUBJECTS

Forty one ADHD cases were diagnosed as per the DSM-IV-TR criteria and evaluated by Conners Parents and Teachers Rating Scale and Wechslers Intelligence Scale for Children.

METHODS

Genomic DNA was amplified for exon 2 *444g/a and intron 5 (Taq I) polymorphism in the DBH gene followed by restriction fragment length polymorphism (RFLP) analysis. Haplotype-based haplotype relative risk (HHRR) was analyzed to ascertain the transmission pattern of these two polymorphisms in ADHD cases. Linkage disequilibrium (LD) between the two polymorphisms was calculated using EH+ and 2LD programs.

RESULTS

In the limited number of samples analyzed, a slight increase in transmission of the 444a allele in ADHD subjects was observed for DBH 444g/a. The intron 5 (Taq I) polymorphism showed no significant association with ADHD in these cases. Strong disequilibrium was observed between DBH444g/a and intron 5 (Taq I) polymorphism.

CONCLUSION

This is the first molecular genetic study on ADHD in Indian subjects exploring transmission of polymorphisms in the DBH gene. Preliminary investigation shows a trend towards association between the transmission of DBH444a allele and ADHD. No association was noticed between transmission of intron 5 (Taq I) polymorphism and ADHD in the Indian subjects. Presence of strong LD may point towards co-segregation of these two polymorphisms more often than expected.

摘要

目的

研究印度注意缺陷多动障碍（ADHD）病例中注意缺陷多动障碍与多巴胺β羟化酶（DBH）基因多态性之间的关联。

对象

41例ADHD病例根据《精神疾病诊断与统计手册》第四版修订版（DSM-IV-TR）标准进行诊断，并通过康纳斯父母与教师评定量表以及韦氏儿童智力量表进行评估。

方法

对DBH基因的外显子2 *444g/a和内含子5（Taq I）多态性进行基因组DNA扩增，随后进行限制性片段长度多态性（RFLP）分析。基于单倍型的单倍型相对风险（HHRR）进行分析，以确定这两种多态性在ADHD病例中的传递模式。使用EH+和2LD程序计算这两种多态性之间的连锁不平衡（LD）。

结果

在分析的有限数量样本中，观察到DBH 444g/a的444a等位基因在ADHD受试者中的传递略有增加。内含子5（Taq I）多态性在这些病例中与ADHD无显著关联。观察到DBH444g/a与内含子5（Taq I）多态性之间存在强不平衡。

结论

这是对印度受试者ADHD进行的首次分子遗传学研究，探索DBH基因多态性的传递。初步调查显示DBH444a等位基因传递与ADHD之间存在关联趋势。在印度受试者中，未发现内含子5（Taq I）多态性传递与ADHD之间存在关联。强LD的存在可能表明这两种多态性比预期更常共分离。

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