本文選題：注意缺陷多動障礙 + 表觀遺傳學�。� 參考：《昆明醫(yī)科大學》2016年碩士論文

【摘要】：目的：探索注意缺陷多動障礙(Attention Deficit Hyperactivity Disorder, ADHD)患兒和正常兒童在多巴胺轉運體基因(DAT1/SLC6A3基因)、多巴胺D 4受體基因(DRD4基因)啟動子區(qū)CpG島甲基化狀態(tài)的差異,并了解DAT1、DRD4基甲基化水平與ADHD患兒臨床癥狀嚴重程度的相關性,旨在從表觀遺傳學角度進一步了解和闡明ADHD患病的遺傳學機制、以及臨床癥狀和多巴胺神經遞質系統(tǒng)甲基化水平之間的關系。方法：收集111例ADHD患者及118例對照組兒童的外周血及一般人口學資料,同時對11 1例ADHD患者的臨床癥狀、認知功能、家族史進行評定。采用亞硫酸氫鈉測序法,明確111例ADHD患者及118例對照兒童的DAT1基因、DRD4基因的啟動子區(qū)CpG島目標片段中每一個CpG位點的甲基化狀態(tài)。結果：1、病例組和對照組在DAT1和DRD4基因啟動子區(qū)總體發(fā)生甲基化的頻數(shù)比例的比較中差異均無統(tǒng)計學意義(P0.05);DAT1基因啟動子區(qū)CpG島片段中,第17個CpG位點病例組發(fā)生甲基化的頻數(shù)比例較對照組高(P0.05); DRD4基因啟動子區(qū)CpG島片段中,第8個CpG位點病例組發(fā)生甲基化的頻數(shù)比例較對照組高(P0.05)；2、在所有樣本中,DAT1基因啟動子區(qū)發(fā)生甲基化的頻數(shù)比例為男性高于女性(P0.05), DRD4基因啟動子區(qū)發(fā)生甲基化頻數(shù)的比例則為女性高于男性(P0.05)；病例組中DAT1基因啟動子區(qū)發(fā)生甲基化的頻數(shù)比例為男性高于女性(P0.05)；對照組中DRD4基因啟動子區(qū)發(fā)生甲基化的頻數(shù)比例為女性高于男性(P0.05)。3、在所有樣本中,7歲年齡組在DAT1基因啟動子區(qū)發(fā)生甲基化的頻數(shù)比例高于1-7歲組(P0.05)；病例組中7歲年齡組在DAT1基因啟動子區(qū)發(fā)生甲基化的頻數(shù)比例亦高于1-7歲組(P0.05)；病例組中病程4年組在DAT1基因啟動子區(qū)發(fā)生甲基化的頻數(shù)比例高于病程為1-4年組的ADHD患者(P0.05)。4.病例組中,無抑郁、焦慮、ADHD家族史的患者其DAT1啟動子區(qū)甲基化頻數(shù)比例高于有相關家族史的患者(P0.05)。5.病例組中,對立違抗障礙量表(oppositional defiant disorder, ODD)9分的患兒其DAT1基因甲基化頻數(shù)比例較ODD量表得分≥9分的患兒高,且DAT1基因甲基化率與ODD量表得分呈負相關(P均0.05);DAT1和DRD4基因甲基化頻數(shù)比例在ADHD-RS-Ⅳ (ADHD評估量表)總分(g0分組與30分組)、注意缺陷分(≤17分組與17分組)、多動沖動分(≤13分組與13分組)以上兩兩組間的比較中均未檢出統(tǒng)計學差異(P均0.05)。結論：1.DAT1及DRD4基因啟動子區(qū)CpG島甲基化狀態(tài)可能與ADHD易感性相關；2.不同性別、年齡DAT1及DRD4基因啟動子區(qū)CpG島甲基化狀態(tài)存在差異；3.DAT1基因啟動子區(qū)甲基化水平可能影響ADHD患者對立違抗行為的嚴重程度。
[Abstract]:Objective: to explore the difference of methylation status between children with attention deficit hyperactivity disorder (ADHDD) and normal children in the promoter of dopamine transporter gene (DAT1 / SLC6A3) and dopamine D4 receptor gene (DRD4) promoter.To understand the correlation between the level of DAT1 DRD4 methylation and the severity of clinical symptoms in children with ADHD, the purpose of this study was to further understand and elucidate the genetic mechanism of ADHD from the perspective of epigenetics.And the relationship between clinical symptoms and methylation level of dopamine neurotransmitter system.Methods: the peripheral blood and general demographic data of 111 ADHD patients and 118 control children were collected, and the clinical symptoms, cognitive function and family history of 111 patients with ADHD were evaluated.Sodium bisulfite sequencing was used to determine the methylation status of each CpG site in the CpG island of the promoter region of the DAT1 gene in 111 ADHD patients and 118 control children.Results there was no significant difference between the case group and the control group in the frequency of total methylation in the promoter region of DAT1 and DRD4 gene. There was no significant difference between the two groups in the CpG island fragment of the promoter region of P0.05DAT1 gene.The frequency of methylation in the 17th CpG locus group was higher than that in the control group, and in the CpG island fragment of the promoter region of the DRD4 gene, the frequency of methylation was higher than that in the control group.The frequency of methylation in the eighth CpG locus group was higher than that in the control group. The frequency of methylation in the promoter region of DAT1 gene was higher in males than in females, and the frequency of methylation in promoter region of DRD4 gene was higher in males than in females.The frequency of methylation in the promoter region of DAT1 gene was higher in the male than in the female, and the frequency of methylation in the promoter of the DRD4 gene in the control group was higher than that in the male.In all the samples, the frequency of methylation in the promoter region of DAT1 gene was higher in the age group of 7 years old than that in the group of 1-7 years old, and in the age group of 7 years old, the frequency of methylation in the promoter region of the DAT1 gene group was higher than that in the group of 1-7 years old, and that in the age group of 7 years old was higher than that in the group of 1-7 years old.The frequency of methylation in the promoter region of DAT1 gene in the 4-year course group was higher than that in the ADHD group with a duration of 1-4 years (P0.05. 4).In the case group, the frequency of methylation in the DAT1 promoter was higher in the patients without depression and anxiety than in the patients with a family history (P 0.05. 5).In the case group, the proportion of DAT1 gene methylation frequency in children with oppositional defiant disorder (ODD9) scores was higher than those with ODD 鈮，

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