Multicenter Analysis of the SLC6A3/DAT1 VNTR Haplotype in Persistent ADHD Suggests Differential Involvement of the Gene in Childhood and Persistent ADHD

被引：153

作者：

Franke, Barbara ^{[1
,2
]}

Vasquez, Alejandro Arias ^{[1
,2
]}

Johansson, Stefan ^{[3
,4
]}

Hoogman, Martine ^{[2
]}

Romanos, Jasmin ^{[5
]}

Boreatti-Huemmer, Andrea ^{[5
]}

Heine, Monika ^{[5
]}

Jacob, Christian P. ^{[5
]}

Lesch, Klaus-Peter ^{[5
,6
]}

Casas, Miguel ^{[7
,8
]}

Ribases, Marta ^{[7
]}

Bosch, Rosa ^{[7
]}

Sanchez-Mora, Cristina ^{[7
]}

Gomez-Barros, Nuria ^{[7
]}

Fernandez-Castillo, Noelia ^{[9
]}

Bayes, Monica ^{[10
,11
,12
]}

Halmoy, Anne ^{[3
]}

Halleland, Helene ^{[13
]}

Landaas, Elisabeth T. ^{[3
,4
]}

Fasmer, Ole B. ^{[14
,15
]}

Knappskog, Per M. ^{[4
,15
]}

Heister, Angelien J. G. A. M. ^{[1
]}

Kiemeney, Lambertus A. ^{[16
]}

Kooij, J. J. Sandra ^{[17
]}

Boonstra, A. Marije ^{[17
]}

Kan, Cees C. ^{[2
]}

Asherson, Philip ^{[18
]}

Faraone, Stephen V. ^{[19
,20
]}

Buitelaar, Jan K. ^{[2
]}

Haavik, Jan ^{[3
,14
]}

Cormand, Bru ^{[21
,22
]}

Antoni Ramos-Quiroga, Josep ^{[7
,8
]}

Reif, Andreas ^{[5
,6
]}

机构：

[1] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands

[2] Radboud Univ Nijmegen, Med Ctr, Ctr Neurosci, Donders Inst Brain Cognit & Behav,Dept Psychiat, NL-6500 HB Nijmegen, Netherlands

[3] Univ Bergen, Dept Biomed, Bergen, Norway

[4] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway

[5] Univ Wurzburg, Dept Psychiat & Psychotherapy, Wurzburg, Germany

[6] Univ Wurzburg, Interdiciplinary Ctr Clin Res, IZKF, Wurzburg, Germany

[7] Hosp Univ Vall Hebron, Dept Psychiat, Barcelona, Catalonia, Spain

[8] Univ Autonoma Barcelona, Dept Psychiat & Legal Med, Catalonia, Spain

[9] Univ Barcelona, Fac Biol, Dept Genet, Catalonia, Spain

[10] UPF, CRG, Genes & Dis Program, Barcelona, Catalonia, Spain

[11] CRG, Inst Salud Carlos III, CIBER Epidemiol & Salud Publ, Barcelona, Catalonia, Spain

[12] Ctr Nacl Genotipado CeGen, Barcelona, Catalonia, Spain

[13] Univ Bergen, Dept Biol & Med Psychol, Bergen, Norway

[14] Haukeland Hosp, Dept Psychiat, N-5021 Bergen, Norway

[15] Univ Bergen, Dept Clin Med, Bergen, Norway

[16] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol & Biostat, NL-6500 HB Nijmegen, Netherlands

[17] Program Adult ADHD, Psychomed Programs, PsyQ, The Hague, Netherlands

[18] Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat, London WC2R 2LS, England

[19] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA

[20] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA

[21] Inst Salud Carlos III, CIBER Enfermedades Raras, Barcelona, Catalonia, Spain

[22] Univ Barcelona, Inst Biomed, Catalonia, Spain

来源：

NEUROPSYCHOPHARMACOLOGY | 2010年 / 35卷 / 03期

关键词：

dopamine; transporters; psychiatry and behavioral sciences; neurogenetics; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY-DISORDER; DOPAMINE TRANSPORTER GENE; COMORBIDITY SURVEY REPLICATION; AGE-DEPENDENT DECLINE; COMMON HAPLOTYPE; SYSTEM GENES; ADULT ADHD; DAT1; GENE; ASSOCIATION;

D O I：

10.1038/npp.2009.170

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Attention deficit/hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders with a worldwide prevalence around 4-5% in children and 1-4% in adults. Although ADHD is highly heritable and familial risk may contribute most strongly to the persistent form of the disorder, there are few studies on the genetics of ADHD in adults. In this paper, we present the first results of the International Multicentre Persistent ADHD Genetics CollaboraTion (IMpACT) that has been set up with the goal of performing research into the genetics of persistent ADHD. In this study, we carried out a combined analysis as well as a meta-analysis of the association of the SLC6A3/DAT1 gene with persistent ADHD in 1440 patients and 1769 controls from IMpACT and an earlier report. DAT1, encoding the dopamine transporter, is one of the most frequently studied genes in ADHD, though results have been inconsistent. A variable number tandem repeat polymorphism (VNTR) in the 3'-untranslated region (UTR) of the gene and, more recently, a haplotype of this VNTR with another VNTR in intron 8 have been the target of most studies. Although the 10/10 genotype of the 3'-UTR VNTR and the 10-6 haplotype of the two VNTRs are thought to be risk factors for ADHD in children, we found the 9/9 genotype and the 9-6 haplotype associated with persistent ADHD. In conclusion, a differential association of DAT1 with ADHD in children and in adults might help explain the inconsistencies observed in earlier association studies. However, the data might also imply that DAT1 has a modulatory rather than causative role in ADHD. Neuropsychopharmacology (2010) 35, 656-664; doi:10.1038/npp.2009.170; published online 4 November 2009

引用

页码：656 / 664

页数：9

共 49 条

[1]

[Anonymous], REV MAN REVMAN

[2] Confirmation that a specific haplotype of the dopamine transporter gene is associated with combined-type ADHD [J].

Asherson, Philip ;

Brookes, Keeley ;

Franke, Barbara ;

Chen, Wai ;

Gill, Michael ;

Ebstein, Richard P. ;

Buitelaar, Jan ;

Banaschewski, Tobias ;

Sonuga-Barke, Edmund J. S. ;

Eisenberg, Jacques ;

Manor, Iris ;

Miranda, Ana ;

Oades, Robert D. ;

Roeyers, Herbert ;

Rothenberger, Aribert ;

Sergeant, Joseph ;

Steinhausen, Hans-Christoph ;

Faraone, Stephen V. .

AMERICAN JOURNAL OF PSYCHIATRY, 2007, 164 (04) :674-677

[3] Young adult outcome of hyperactive children: Adaptive functioning in major life activities [J].

Barkley, RA ;

Fischer, M ;

Smallish, L ;

Fletcher, K .

JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY, 2006, 45 (02) :192-202

[4] An examination of the behavioral and neuropsychological correlates of three ADHD candidate gene polymorphisms (DRD4 7+, DBH TaqI A2, and DAT1 40 bp VNTR) in hyperactive and normal children followed to adulthood [J].

Barkley, Russell A. ;

Smith, Karen M. ;

Fischer, Mariellen ;

Navia, Bradford .

AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2006, 141B (05) :487-498

[5] ADHD from a socio-economic perspective [J].

Bernfort, Lars ;

Nordfeldt, Sam ;

Persson, Jan .

ACTA PAEDIATRICA, 2008, 97 (02) :239-245

[6] Epistasis between dopamine regulating genes identifies a nonlinear response of the human hippocampus during memory tasks [J].

Bertolino, Alessandro ;

Di Giorgio, Annabella ;

Blasi, Giuseppe ;

Sambataro, Fabio ;

Caforio, Grazia ;

Sinibaldi, Lorenzo ;

Latorre, Valeria ;

Rampino, Antonio ;

Taurisano, Paolo ;

Fazio, Leonardo ;

Romano, Raffaella ;

Douzgou, Sofia ;

Popolizio, Teresa ;

Kolachana, Bhaskar ;

Nardini, Marcello ;

Weinberger, Daniel R. ;

Dallapiccola, Bruno .

BIOLOGICAL PSYCHIATRY, 2008, 64 (03) :226-234

[7] Age-dependent decline of symptoms of attention deficit hyperactivity disorder: Impact of remission definition and symptom type [J].

Biederman, J ;

Mick, E ;

Faraone, SV .

AMERICAN JOURNAL OF PSYCHIATRY, 2000, 157 (05) :816-818

[8] Association of ADHD with Genetic Variants in the 5′-Region of the Dopamine Transporter Gene: Evidence for Allelic Heterogeneity [J].

Brookes, K. J. ;

Xu, X. ;

Anney, R. ;

Franke, B. ;

Zhou, K. ;

Chen, Wai ;

Banaschewski, T. ;

Buitelaar, J. ;

Ebstein, R. ;

Eisenberg, J. ;

Gill, M. ;

Miranda, A. ;

Oades, R. D. ;

Roeyers, H. ;

Rothenberger, A. ;

Sergeant, J. ;

Sonuga-Barke, E. J. S. ;

Steinhausen, H. -C. ;

Taylor, E. ;

Faraone, S. V. ;

Asherson, P. .

AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2008, 147B (08) :1519-1523

[9] Relationship between VNTR Polymorphisms of the human dopamine transporter gene and expression in post-mortem midbrain tissue [J].

Brookes, Keeley J. ;

Neale, Benjamin M. ;

Sugden, Karen ;

Khan, Nadeem ;

Asherson, Philip ;

D'Souza, Ursula M. .

AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2007, 144B (08) :1070-1078

[10] A common haplotype of the dopamine transporter gene associated with attention-deficit/hyperactivity disorder and interacting with maternal use of alcohol during pregnancy [J].

Brookes, KJ ;

Mill, J ;

Guindalini, C ;

Curran, S ;

Xu, XH ;

Knight, J ;

Chen, CK ;

Huang, YS ;

Sethna, V ;

Taylor, E ;

Chen, W ;

Breen, G ;

Asherson, P .

ARCHIVES OF GENERAL PSYCHIATRY, 2006, 63 (01) :74-81

← 1 2 3 4 5 →