Kopecková Marta, Paclt Ivo, Petrásek Jan, Pacltová Dagmar, Malíková Marcela, Zagatová Veronika
Department of Biology and Medical Genetics, Motol, Prague, Czech Republic.
Neuro Endocrinol Lett. 2008 Apr;29(2):246-51.
Pharmacological approach is the most effective way of treatment of ADHD and its early application prevents from the progress of secondary disorders. The study on present neurotransmitter systems in pathology of ADHD can be helpful in selecting appropriate drug, since there are used various substances with different mechanisms of functioning in treatment of the hyperkinetic syndrome.
Within our study there were selected the genes of dopaminergic (DRD2, DRD3, DAT1), noradrenergic (DBH) and serotoninergic (5-HTT) systems. With the use of molecular-genetic methods based on association strategy "case-control" there were analysed genes including 11 polymorphisms. The presence of risk alleles was examined in comparison of the sample of 100 ADHD children to a control group of another 100 subjects, who were checked by child psychiatrists and examined with the Conners test in order to exclude eventual cases with ADHD symptoms.
Our research suggests the association of some genes with ADHD. It could be concluded: 1) the risk of ADHD is significantly increased in the presence of one risk allele in genes DRD2 (O.R.=7,5), 5-HTT (O.R.=2,7) and DAT1 (O.R.=1,6). 2) The risk of ADHD is significantly increased at homozygotes for risk alleles in genes DRD2 (O.R.=54,8), 5-HTT (O.R.=6,7) and DAT1 (O.R.=6,6). For polymorphisms G444A and C1603T in DBH, which were detected by univariant analysis, haplotype analysis was performed and resulted in conclusion that: 3) the risk of ADHD is significantly increased in the presence of allele DBH +444A as well as in the presence of allele DBH +1603T (O.R.=15).
药物治疗是治疗注意力缺陷多动障碍（ADHD）最有效的方法，早期应用可防止继发疾病的进展。研究ADHD病理中的当前神经递质系统有助于选择合适的药物，因为在治疗多动综合征时使用了各种作用机制不同的物质。
在我们的研究中，选择了多巴胺能（DRD2、DRD3、DAT1）、去甲肾上腺素能（DBH）和5-羟色胺能（5-HTT）系统的基因。使用基于“病例对照”关联策略的分子遗传学方法，分析了包括11种多态性的基因。将100名ADHD儿童的样本与另100名受试者的对照组进行比较，检查风险等位基因的存在，这100名受试者由儿童精神科医生检查，并通过康纳斯测试进行检查，以排除最终患有ADHD症状的病例。
我们的研究表明某些基因与ADHD有关联。可以得出以下结论：1）DRD2基因（优势比=7.5）、5-HTT基因（优势比=2.7）和DAT1基因（优势比=1.6）存在一个风险等位基因时，ADHD风险显著增加。2）DRD2基因（优势比=54.8）、5-HTT基因（优势比=6.7）和DAT1基因（优势比=6.6）的风险等位基因纯合子时，ADHD风险显著增加。对于单变量分析检测到的DBH基因中的G444A和C1603T多态性，进行了单倍型分析，得出结论：3）存在DBH +444A等位基因以及存在DBH +1603T等位基因时，ADHD风险显著增加（优势比=15）。
