目的 进一步探讨多巴胺D4受体(DRD4)基因第三外显子48 bp可变重复序列(VNTR)多态性与注意缺陷多动障碍(ADHD)儿童青少年的相关情况。方法 通过中国知网(CNKI)、万方、维普、中国生物医学文献数据库(CBM)、PubMed、Cochrane Library、EBSCO、Ovid、Springer数据库,检索国内外关于DRD4基因第3外显子48 bp VNTR多态性与儿童ADHD关联性的病例对照研究,采用Meta分析综合定量分析纳入文献。结果 20篇文献共纳入3 658例ADHD患者和6 272例对照,Meta分析结果提示在总人群中4R、7R和长片段ADHD组与对照组相比差异均有统计学意义,其他片断ADHD组与对照组相比差异均无统计学意义。亚洲人群中各种重复片段的ADHD组与对照组相比差异均无统计学意义。非亚洲人群中4R、7R、短片断和长片段(＞4R)ADHD组与对照组相比差异均有统计学意义,其余重复片段差异均无统计学意义。结论 Meta分析显示总人群DRD4 48 bp 4R、7R、长片段(＞4R)与ADHD间有相关性;非亚洲人群DRD4 48 bp4R、7R、短片段、长片段(＞4R)与ADHD间有相关性;亚洲人群48 bp VNTR多态性与ADHD间均未显示有相关性。
Abstract
Objective To explore the association of the 48 bp variable number of tandem repeat(VNTR) polymorphism at exon 3 of dopamine D4 receptor (DRD4) gene with attention deficit hyperactivity disorder (ADHD). Methods The Chinese and English references about the association between 48 bp VNTR polymorphism of DRD4 gene and ADHD were retrieved through Chinese National Knowledge Infrastructure (CNKI),Wanfang,Weipu,Chinese Biomedical Database( CBM),PubMed,Cochrane Library,EBSCO,Ovid,Springer databases,until October 30,2015.A Meta-analysis was used to systematically analyze the literatures. Results A total of 20 studies were included in the final Meta-analysis,enrolling a total of 3 658 ADHD cases and 6 272 controls.The Meta-analysis showed that the frequencies of DRD4 gene 48 bp 4 repeat (4R),7 repeat (7R) and long repeat had statistical differences between ADHD group and the control group in the global group;the frequencies of DRD4 gene 48 bp had not statistical difference between ADHD group and the control group in the Asia group ;the frequencies of DRD4 gene 48 bp 4R,7R,short repeat and long repeat had statistical differences in the non-Asia group. Conclusions The Meta-analysis revealed that the DRD4 48 bp 4R,7R and long repeat have association with ADHD in the global group;The DRD4 48 bp 4R,7R,short repeat and long repeat have association with ADHD in the global group in non-Asia group.There is no statistical difference between ADHD group and the control group in the Asia group.
关键词
注意缺陷多动障碍 /
多巴胺D4受体基因 /
可变重复序列 /
Meta分析 /
儿童
Key words
attention deficit hyperactivity disorder /
dopamine D4 receptor gene /
variable number of tandem repeat /
Meta analysis /
children
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] 童连,史慧静,臧嘉捷.中国儿童ADHD流行状况Meta分析[J].中国公共卫生,2013,29(9):1279-1283.
[2] Faraone SV,Perlis RH,Doyle AE,et al.Molecular genetics of attention-deficit/hyperactivity disorder[J].Biological Psychiatry,2005,57(11):1313-1323.
[3] Oak JN,Oldenhof J,Van Tol HHM.The dopamine D4 receptor:one decade of research[J].European Journal of Pharmacology,2000,405(1-3):303-327.
[4] Bhaduri N,Das M,Sinha S,et al.Association of dopamine D4 receptor (DRD4) polymorphisms with attention deficit hyperactivity disorder in Indian population[J].Am J Med Genet B Neuropsychiatr Genet,2006,141b(1):61-66.
[5] Leung PW,Lee CC,Hung SF,et al.Dopamine receptor D4 (DRD4) gene in Han Chinese children with attention-deficit/hyperactivity disorder (ADHD):increased prevalence of the 2-repeat allele[J].Am J Med Genet B Neuropsychiatr Genet,2005,133b(1):54-56.
[6] Carrasco X,Rothhammer P,Moraga M,et al.Genotypic interaction between DRD4 and DAT1 loci is a high risk factor for attention-deficit/hyperactivity disorder in Chilean families[J].American Journal of Medical Genetics.Part B,Neuropsychiatric Genetics:2006,141b(1):51-54.
[7] Castellanos FX,Lau E,Tayebi N,et al.Lack of an association between a dopamine-4 receptor polymorphism and attention-deficit/hyperactivity disorder:genetic and brain morphometric analyses[J].Molecular Psychiatry,1998,3(5):431-434.
[8] Cheuk DKL,Li SYH,Wong V.Exon 3 polymorphisms of dopamine D4 receptor (DRD4) gene and attention deficit hyperactivity disorder in Chinese[J].Children American Journal of Medical Genetics:Neuropsychiatric Genetics,2006,141b(8):907-911.
[9] Comings DE,Gonzalez N,Wu S,et al.Studies of the 48 bp repeat polymorphism of the DRD4 gene in impulsive,compulsive,addictive behaviors:Tourette syndrome,ADHD,pathological gambling,and substance abuse[J].American Journal of Medical Genetics,1999,88(4):358-368.
[10] Das M,Bhowmik AD,Bhaduri N,et al.Role of gene-gene/gene-environment interaction in the etiology of eastern Indian ADHD probands[J].Progress in Neuro-Psychopharmacology and Biological Psychiatry,2011,35(2):577-587.
[11] Gabriela ML,John DG,Magdalena BV,et al.Genetic interaction analysis for DRD4 and DAT1 genes in a group of Mexican ADHD patients[J].Neurosci Lett,2009,451(3):257-260.
[12] Hawi Z,McCarron M,Kirley A,et al.No association of the dopamine DRD4 receptor (DRD4) gene polymorphism with attention deficit hyperactivity disorder (ADHD) in the Irish population[J].American Journal of Medical Genetics,2000,96(3):268-272.
[13] Holmes J,Payton A,Barrett JH,et al.A family-based and case-control association study of the dopamine D4 receptor gene and dopamine transporter gene in attention deficit hyperactivity disorder[J].Molecular Psychiatry,2000,5(5):523-530.
[14] Johnson KA,Kelly SP,Robertson IH,et al.Absence of the 7-repeat variant of the DRD4 VNTR is associated with drifting sustained attention in children with ADHD but not in controls[J].American Journal of Medical Genetics Part B,Neuropsychiatric Genetics,2008,147b(6):927-937.
[15] LaHoste GJ,Swanson JM,Wigal SB,et al.Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder[J].Molecular Psychiatry,1996,1(2):121-124.
[16] Maitra S,Sarkar K,Ghosh P,et al.Potential contribution of dopaminergic gene variants in ADHD core traits and co-morbidity:a study on eastern Indian probands[J].Cellular And Molecular Neurobiology,2014,34(4):549-564.
[17] Mill J,Curran S,Kent L,et al.Attention deficit hyperactivity disorder (ADHD) and the dopamine D4 receptor gene:evidence of association but no linkage in a UK sample[J].Molecular Psychiatry,2001,6(4):440-444.
[18] Roman T,Schmitz M,Polanczyk G,et al.Attention-deficit hyperactivity disorder:a study of association with both the dopamine transporter gene and the dopamine D4 receptor gene[J].American Journal of Medical Genetics,2001,105(5):471-478.
[19] Rowe DC,Stever C,Giedinghagen LN,et al.Dopamine DRD4 receptor polymorphism and attention deficit hyperactivity disorder[J].Molecular Psychiatry,1998,3(5):419-426.
[20] Swanson JM,Sunohara GA,Kennedy JL,et al.Association of the dopamine receptor D4 (DRD4) gene with a refined phenotype of attention deficit hyperactivity disorder (ADHD):a family-based approach[J].Molecular Psychiatry,1998,3(1):38-41.
[21] 陈智,经承学,陈萍,等.多巴胺D4受体基因多态性与注意缺陷多动障碍的关联研究[J].中国现代医学杂志,2007,17(16):1954-1958.
[22] 钱秋谨,王玉凤,李君,等.注意缺陷多动障碍与多巴胺D4受体和多巴胺载体蛋白基因多态性的关系[J].北京大学学报:医学版,2003,35(4):412-418.
[23] 赵爱玲,苏林雁,罗学荣,等.多巴胺D4受体基因与注意缺陷多动障碍及其相关症状的关联分析[J].中国行为医学科学,2005,14(3):199-201.
[24] Fayyad J,De Graaf R,Kessler R,et al.Cross-national prevalence and correlates of adult attention-deficit hyperactivity disorder[J].British Journal of Psychiatry,2007,190(5):402-409.
[25] Smith TF.The Meta-analysis of the heterogeneity in association of DRD4 7-repeat allele and AD/HD:stronger association with AD/HD combined type[J].American Journal of Medical Genetics:Part B,Neuropsychiatric Genetics,2010,153b(6):1189-1199.
PDF(642 KB)
