Association of the Dopamine Transporter (SLC6A3/DAT1) Gene 9-6 Haplotype With Adult ADHD

被引:70
作者
Franke, B. [1 ,2 ]
Hoogman, M. [1 ]
Vasquez, A. Arias [1 ,2 ,3 ]
Heister, J. G. A. M. [2 ]
Savelkoul, P. J. [1 ]
Naber, M. [2 ]
Scheffer, H. [2 ]
Kiemeney, L. A. [3 ]
Kan, C. C. [1 ]
Kooij, J. J. S. [4 ]
Buitelaar, J. K. [1 ]
机构
[1] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Donders Inst Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands
[2] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands
[3] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol & Biostat, NL-6500 HB Nijmegen, Netherlands
[4] Psychomed Programs, PsyQ, The Hague, Netherlands
关键词
persistent ADHD; association study; variable number of tandem repeats (VNTR); DAT1; intron; 8; VNTR; 3;
D O I
10.1002/ajmg.b.30861
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
ADHD is a neuropsychiatric disorder characterized by chronic hyperactivity, inattention and impulsivity, which affects about 5% of school-age children. ADHD persists into adulthood in at least 15% of cases. It is highly heritable and familial influences seem strongest for ADHD persisting into adulthood. However, most of the genetic research in ADHD has been carried out in children with the disorder. The gene that has received most attention in ADHD genetics is SLC6A3/DAT1 encoding the dopamine transporter. In the current study we attempted to replicate in adults with ADHD the reported association of a 10-6 SLC6A3-haplotype, formed by the 10-repeat allele of the variable number of tandem repeat (VNTR) polymorphism in the 3' untranslated region of the gene and the 6-repeat allele of the VNTR in intron 8 of the gene, with childhood ADHD. In addition, we wished to explore the role of a recently described VNTR in intron 3 of the gene. Two hundred sixteen patients and 528 controls were included in the study. We found a 9-6 SLC6A3-haplotype, rather than the 10-6 haplotype, to be associated with ADHD in adults. The intron 3 VNTR showed no association with adult ADHD. Our findings converge with earlier reports and suggest that age is an important factor to be taken into account when assessing the association of SLC6A3 with ADHD. If confirmed in other studies, the differential association of the gene with ADHD in children and in adults might imply that SLC6A3 plays a role in modulating the ADHD phenotype, rather than causing it. (C) 2008 Wiley-Liss, Inc.
引用
收藏
页码:1576 / 1579
页数:4
相关论文
共 24 条
[1]   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
[2]   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
[3]   Disentangling deficits in adults with attention-deficit/hyperactivity disorder [J].
Bekker, EM ;
Overtoom, CCE ;
Kooij, JJS ;
Buitelaar, JK ;
Verbaten, MN ;
Kenemans, JL .
ARCHIVES OF GENERAL PSYCHIATRY, 2005, 62 (10) :1129-1136
[4]   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
[5]   An exploratory study of the relationship between four candidate genes and neurocognitive performance in adult ADHD [J].
Boonstra, A. Marije ;
Kooij, J. J. Sandra ;
Buitelaar, Jan K. ;
Oosterlaan, Jaap ;
Sergeant, Joseph A. ;
Heister, J. G. A. M. Angelien ;
Franke, Barbara .
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2008, 147B (03) :397-402
[6]   The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder:: association signals in DRD4, DAT1 and 16 other genes [J].
Brookes, K. ;
Xu, X. ;
Chen, W. ;
Zhou, K. ;
Neale, B. ;
Lowe, N. ;
Aneey, R. ;
Franke, B. ;
Gill, M. ;
Ebstein, R. ;
Buitelaar, J. ;
Sham, P. ;
Campbell, D. ;
Knight, J. ;
Andreou, P. ;
Altink, M. ;
Arnold, R. ;
Boer, F. ;
Buschgens, C. ;
Butler, L. ;
Christiansen, H. ;
Feldman, L. ;
Fleischman, K. ;
Fliers, E. ;
Howe-Forbes, R. ;
Goldfarb, A. ;
Heise, A. ;
Gabriels, I. ;
Korn-Lubetzki, I. ;
Marco, R. ;
Medad, S. ;
Minderaa, R. ;
Mulas, F. ;
Mueller, U. ;
Mulligan, A. ;
Rabin, K. ;
Rommelse, N. ;
Sethna, V. ;
Sorohan, J. ;
Uebel, H. ;
Psychogiou, L. ;
Weeks, A. ;
Barrett, R. ;
Craig, I. ;
Banaschewski, T. ;
Sonuga-Barke, E. J. S. ;
Eisenberg, J. ;
Kuntsi, J. ;
Manor, I. ;
McGuffin, P. .
MOLECULAR PSYCHIATRY, 2006, 11 (10) :934-953
[7]   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
[8]   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
[9]  
Brüggemann D, 2007, PSYCHIAT GENET, V17, P121
[10]   Impact of the COMT Val108/158 Met and DAT genotypes on prefrontal function in healthy subjects [J].
Caldu, Xavier ;
Vendrell, Pere ;
Bartres-Faz, David ;
Clemente, Inmaculada ;
Bargallo, Nuria ;
Jurado, Maria Angeles ;
Serra-Grabulosa, Josep Maria ;
Junque, Carme .
NEUROIMAGE, 2007, 37 (04) :1437-1444