评估注意缺陷多动障碍儿童DRD4基因Ex3 vNTR和rs3758653多态性与哌甲酯剂量的关系

S. Amiri, Sardari Mamaghani Negar, S. Farhang, Sima Mansouri Derakhshan, M. Shekari Khaniani, Leila Mehdizadeh Fanid
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After performing polymerase chain reaction (PCR), the products were separated using specific restriction enzymes and then polymorphisms of Ex3 VNTR and rs3758653 of DRD4 gene were analyzed in 2% agarose gel. The last dose to achieve the therapeutic response was recorded in mg/kg. Then, we investigated the relationship between the doses of drug used to achieve the therapeutic response and the existence of the mentioned polymorphisms. Results. There was no significant relationship between treatment response and type of polymorphism. Also, there was no significant relationship between the average dose of drug and the polymorphisms of three replicates, four replicates, six replicates, and more than six replicates in EX3VNTR in DRD4 gene. In addition, we witnessed no statistically significant relationship between the mean drug dose and CC, TC, and TT genotypes in DRD4rs3758653. Conclusion. There was no significant relationship between treatment response and type of polymorphism. 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摘要

背景。注意缺陷多动障碍(ADHD)是一种最常见的精神疾病,从早期开始,表现为注意缺陷多动障碍和冲动。本研究旨在研究DRD4基因的分子改变,该基因在先前的研究中与哌醋甲酯剂量有关。方法。研究人群包括2017年在大不里士Bozorgmehr精神病诊所转诊的所有需要药物治疗的5-18岁ADHD患者,为期一年。诊断后,使用Conners ADHD评估量表评估症状严重程度。然后,每个人采集血样4ml,用盐析法提取DNA。经聚合酶链反应(PCR)后,用特异性限制性内切酶分离产物,在2%琼脂糖凝胶中分析DRD4基因Ex3 VNTR和rs3758653的多态性。达到治疗效果的最后剂量以mg/kg记录。然后,我们研究了用于实现治疗反应的药物剂量与上述多态性的存在之间的关系。结果。治疗效果与多态性类型无显著相关。DRD4基因EX3VNTR中3个重复、4个重复、6个重复和6个以上重复的多态性与平均用药剂量无显著关系。此外,我们发现DRD4rs3758653的平均药物剂量与CC、TC和TT基因型之间没有统计学意义的关系。结论。治疗效果与多态性类型无显著相关。DRD4基因EX3VNTR中3个重复、4个重复、6个重复和6个以上重复的多态性与平均用药剂量无显著关系。DRD4rs3758653的平均用药剂量与CC、TC、TT基因型之间无统计学意义。实际意义。通过服用哌甲酯来确定ADHD症状的减轻程度,评估DRD4多态性是否存在与药物剂量的关系,以达到更好的治疗效果,可以收集足够的证据,根据ADHD患者DRD4基因的分子分析来确定哌甲酯的剂量。这可以减少看医生的次数,节省时间,减少药物的副作用。
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Evaluating the relationship between Ex3 vNTR and rs3758653 polymorphisms in DRD4 genes in children with attention deficit hyperactivity disorder with respect to the dose of methylphenidate
Background. Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders starting at an early age with symptoms of attention deficit hyperactivity disorder and impulsivity. This study aimed to investigate the molecular alterations of the DRD4 gene, which have been linked to ADHD in previous studies with respect to the dose of methylphenidate. Methods. The study population included all ADHD patients needing drug therapy aged 5-18 years referred to Bozorgmehr psychiatric clinic in Tabriz in 2017 for one year. After diagnosis, symptoms severity was assessed using the Conners Scale for ADHD Assessment. Then, 4 ml of blood was collected from each individual and DNA was extracted using salting out method. After performing polymerase chain reaction (PCR), the products were separated using specific restriction enzymes and then polymorphisms of Ex3 VNTR and rs3758653 of DRD4 gene were analyzed in 2% agarose gel. The last dose to achieve the therapeutic response was recorded in mg/kg. Then, we investigated the relationship between the doses of drug used to achieve the therapeutic response and the existence of the mentioned polymorphisms. Results. There was no significant relationship between treatment response and type of polymorphism. Also, there was no significant relationship between the average dose of drug and the polymorphisms of three replicates, four replicates, six replicates, and more than six replicates in EX3VNTR in DRD4 gene. In addition, we witnessed no statistically significant relationship between the mean drug dose and CC, TC, and TT genotypes in DRD4rs3758653. Conclusion. There was no significant relationship between treatment response and type of polymorphism. There was no significant relationship between the average dose of drug and the polymorphisms of three replicate, four replicates, six replicates and more than six replicates in EX3VNTR in DRD4 gene. Between mean drug dose and CC, TC and TT genotypes in DRD4rs3758653, there was no statistically significant relationship. Practical Implications. Determining the reduction of ADHD symptoms by taking methylphenidate and evaluating the relationship between presence or absence of DRD4 polymorphisms and the dosage of drug to achieve a better response to treatment can collect enough evidence to determine the dose of methylphenidate according to the molecular analysis of DRD4 gene in patients with ADHD. This can reduce doctor visits, save time, and decrease the drug side effects.
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