A meta-analysis of association studies between the 10-repeat allele of a VNTR polymorphism in the 3′-UTR of dopamine transporter gene and attention deficit hyperactivity disorder

American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

Volumn 144, Issue 4, 2007, Pages 541-550

  Yang, Binrang ^a   Chan, Raymond C K ^a,b   Jing, Jin ^a   Li, Tao ^c,e   Sham, Pak ^d,e   Chen, Ronald Y L ^d  

^a SUN YAT SEN UNIVERSITY   (China)

^b INSTITUTE OF PSYCHOLOGY   (China)

^c SICHUAN UNIVERSITY   (China)

^d UNIVERSITY OF HONG KONG   (Hong Kong)

^e MEDICAL RESEARCH COUNCIL   (United Kingdom)

Author keywords

ADHD; DAT; TDT

Indexed keywords

DOPAMINE TRANSPORTER;

ALLELE; ATTENTION DEFICIT DISORDER; DAT1 GENE; GENE; GENE MUTATION; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HAPLOTYPE; HUMAN; PRIORITY JOURNAL; REVIEW; SYSTEMATIC REVIEW; UNTRANSLATED REGION; VARIABLE NUMBER OF TANDEM REPEAT;

3' UNTRANSLATED REGIONS; ADOLESCENT; ALLELES; ATTENTION DEFICIT DISORDER WITH HYPERACTIVITY; CASE-CONTROL STUDIES; CHILD; CHILD, PRESCHOOL; DOPAMINE PLASMA MEMBRANE TRANSPORT PROTEINS; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MINISATELLITE REPEATS; ODDS RATIO; POLYMORPHISM, GENETIC;

EID: 34250835846     PISSN: 15524841     EISSN: 1552485X     Source Type: Journal    
DOI: 10.1002/ajmg.b.30453     Document Type: Review

References (95)

1. Asherson P, Virdee V, Curran S, Ebersole L, Freeman B, Craig I, et al. 1998. Association study of DSM-IV attention deficit hyperactivity disorder (ADHD) and monoamine pathway genes. Am J Med Genet 81:549.
2. Bakker SC, van der Meulen EM, Oteman N, Schelleman H, Pearson PL, Buitelaar JK, et al. 2005. DAT1, DRD4, and DRD5 polymorphisms are not associated with ADHD in Dutch families. Am J Med Genet Part B 132B:50-52.
3. Barr CL, Xu C, Kroft J, Feng Y, Wigg K, Zai G, et al. 2001. Haplotype study of three polymorphisms at the dopamine transporter locus confirms linkage to attention-deficit/hyperactivity disorder. Biol Psychiatry 49:333-339.
4. Berlin JA, Laird NM, Sacks HS, Chalmers TC. 1989. A comparison of statistical methods for combining event rates from clinical trials Stat Med 8:141-151.
5. *Bobb AJ, Addington AM, Sidransky E, Gornick MC, Lerch JP, Greenstein DK, et al. 2005. Support for association between ADHD and two candidate genes: NET1 and DRD1. Am J Med Genet Part B 134B:67-72.
6. Borenstein M, Hedges L, Higgins J, Rothstein H. 2005. Comprehensive Meta-analysis Version 2. Biostat. NJ: Englewood.
7. *Brookes KJ, Mill J, Guindalini C, Curran S, Xu XJ, Knight J, et al. 2006. A common haplotype of the dopamine transporter gene associated with attention-deficit/hyperactivity disorder and interacting with maternal use of alcohol during pregnancy. Arch Gen Psychiatry 63:74-81.
8. Cardinal RN, Pennicott DR, Sugathapala CL, Robbins TW, Everitt BJ. 2001. Impulsive choice induced in rats by lesions of the nucleus accumbens core. Science 292:2499-2501.
9. Castellanos FX. 2001. Neuroimaging studies of ADHD. In: Solanto MV, Arnsten AF, Editors. Stimulant drugs and ADHD: Basic and clinical neuroscience. New York: Oxford University Press. p. 243-258.
10. *Chen CK, Chen SL, Mill J, Huang YS, Lin SK, Curran S, et al. 2003. The dopamine transporter gene is associated with attention deficit hyperactivity disorder in a Taiwanese sample. Mol Psychiatry 8:39-396.
11. Cheon KA, Ryu YH, Kim YK, Namkoong K, Kim CH, Lee JD. 2003. Dopamine transporter density in the basal ganglia assessed with [123I]IPT SPECT in children with attention deficit hyperactivity disorder. Eur J Nucl Med Mol Imaging 30:306-311.
12. Cheon KA, Ryu YH, Kim JW, Cho DY. 2005. The homozygosity for 10-repeat allele at dopamine transporter gene and dopamine transporter density in Korean children with attention deficit hyperactivity disorder: Relating to treatment response to methylphenidate. Eur Neuropsychopharmacol 15:95-101.
13. *Cheuk DKL, Li SYH, Wong V. 2006. No Association between VNTR polymorphisms of dopamine transporter gene and attention deficit hyperactivity disorder in Chinese children. Am J Med Genet Part B 141B:123-125.
14. Ciliax BJ, Heilman C, Demchyshyn LL, Pristupa ZB, Ince E, Hersch SM, et al. 1995. The dopamine transporter: Immunochemical characterization and localization in brain. J Neurosci 15:1714-1723.
15. Comings DE, Wu S, Chiu C, Ring RH, Gade R, Ann C, et al. 1996. Polygenic inheritance of Tourette syndrome, stuttering, attention deficit hyperactivity, conduct, and oppositional defiant disorder: The additive and subtractive effect of the three dopaminergic genes-DRD2, D beta H, and DAT1. Am J Med Genet 67:264-288.
16. Conne B, Stutz A, Vassalli JD. 2000. The 3′ untranslated region of messenger RNA: A molecular 'hotspof for pathology? Nat Med 6:637-641.
17. *Cook EH, Stein MA, Krasowski MD, Cox NJ, Olkon DM, Kieffer JE, et al. 1995. Association of attention-deficit disorder and the dopamine transporter gene. Am J Hum Genet 56:993-998.
18. Cooper H, Hedges LV, editors. 1994. The Handbook of Research Synthesis. New York: Russell Sage Foundation.
19. Cragg SJ, Rice ME. 2004. Dancing past the DAT at a DA synapse. Trends Neurosci 27:270-277.
20. Crosbie J, Schachar R. 2001. Deficient inhibition as a marker for familial ADHD. Am J Psychiatry 158:1884-1890.
21. *Curran S, Mill J, Tahir E, Kent L, Richards S, Gould A, et al. 2001. Association study of a dopamine transporter polymorphism and attention deficit hyperactivity disorder in UK and Turkish samples. Mol Psychiatry 6:425-428.
22. Daly G, Hawi Z, Fitzgerald M, Gill M. 1999. Mapping susceptibility loci in attention deficit hyperactivity disorder: Preferential transmission of parental alleles at DAT1, DBH and DRD5 to affected children. Mol Psychiatry 4:192-196.
23. DiMaio S, Grizenko N, Joober R. 2003. Dopamine genes and attention deficit hyperactivity disorder: A review. J Psychiatry Neurosci 28:27-38.
24. Dougherty DD, Bonab AA, Spencer TJ, Rauch SL, Madras BK, Fischman AJ. 1999. Dopamine transporter density in patients with attention deficit hyperactivity disorder. Lancet 354:2132-2133.
25. Dresel S, Krause J, Krause KH, LaFougere C, Brinkbaumer K, Kung HF, et al. 2000. Attention deficit hyperactivity disorder: Binding of [99mTc]TRODAT-1 to the dopamine transporter before and after methylphenidate treatment. Eur J Nucl Med 27:1518-1524.
26. Egger M, Davey Smith G, Schneider M, Minder C. 1997. Bias in meta-analysis detected by a simple, graphical test. Br Med J 315:629-634.
27. Ernst M, Zamekin AJ, Matochik JA, Pascualvaca D, Jons PH, Cohen H. 1999. High midbrain DOPA accumulation in children with attention deficit hyperactivity disorder. Am J Psychiatry 156:1209-1215.
28. Faraone SV, Biederman J. 1998. Neurobiology of attention-deficit hyperactivity disorder. Biol Psychiatry 44:951-958.
29. Faraone SV, Doyle AE. 2000. Genetic influences on attention deficit hyperactivity disorder. Curr Psychiatry Rep 2:143-146.
30. Faraone SV, Perlis RH, Doyle AE, Smoller JW, Goralnick JJ, Holmgren MA, et al. 2005. Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry 57:1313-1323.
31. *Feng Y, Wigg KG, Makkar R, Ickowicz A, Pathare T, Tannock R, et al. 2005. Sequence variation in the 3′-untranslated region of the dopamine transporter gene and attention-deficit hyperactivity disorder (ADHD). Am J Med Genet Part B 139B:1-6.
32. Fuke S, Suo S, Takahashi N, Koike H, Sasagawa N, Ishiura S. 2001. The VNTR polymorphism of the human dopamine transporter (DAT1) gene affects gene expression. Pharmacogenom J 1:152-156.
33. Gainetdinov RR, Caron MG. 2001. Genetics of childhood disorders: XXIV. ADHD, part 8: Hyperdopaminergic mice as an animal model of ADHD. J Am Acad Child Adolesc Psychiatry 40:380-382.
34. Galili-Weisstub E, Levy S, Frisch A, Gross-Tsur V, Michaelovsky E, Kosov A, et al. 2005. Dopamine transporter haplotype and attention-deficit hyperactivity disorder. Mol Psychiatry 10:617-618.
35. Gatley SJ, Volkow ND, Gifford AN, Fowler JS, Dewey SL, Ding YS, et al. 1999. Dopamine-transporter occupancy after intravenous doses of cocaine and methylphenidate in mice and humans. Psychopharmacology 146:93-100.
36. Gill M, Daly G, Heron S, Hawi Z, Fitzgerald M. 1997. Confirmation of association between attention deficit hyperactivity disorder and a dopamine transporter polymorphism. Mol Psychiatry 2:311-313.
37. Giros B, El Mestikawy S, Godinot N, Zheng K, Han H, Yang-Feng T, et al. 1992. Cloning, pharmacological characterization, and chromosome assignment of the human dopamine transporter. Mol Pharmacol 42:383-390.
38. Giros B, Jaber M, Jones SR, Wightman RM, Caron MG. 1996. Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 379:606-612.
39. Granon S, Passetti F, Thomas KL, Dalley JW, Everitt BJ, Robbins TW. 2000. Enhanced and impaired attentional performance after infusion of D1 dopaminergic receptor agents into rat prefrontal cortex. J Neurosci 20:1208-1215.
40. *Hawi Z, Lowe N, Kirley A, Gruenhage F, Nothen M, Greenwood T, et al. 2003. Linkage disequilibrium mapping at DAT1, DRD5 and DBH narrows the search for ADHD susceptibility alleles at these loci. Mol Psychiatry 8:299-308.
41. Heinz A, Goldman D, James DW, Palmour R, Hommer D, Gorey JG, et al. 2000. Genotype influences in vivo dopamine transporter availability in human striatum. Neuropsychopharmacology 22:133-139.
42. *Holmes J, Payton A, Barrett JM, Hever T, Fitzpatrick H, Trumper AL, et al. 2000. A family-based study and case-control association study of the dopamine D4 receptor gene and dopamine transporter gene in attention deficit hyperactivity disorder. Mol Psychiatry 5:523-530.
43. Inoue-Murayama M, Adachi S, Mishima N, Mitani H, Takenaka O, Terao K, et al. 2002. Variation of variable number of tandem repeat sequences in the 3′-untranslated region of primate dopamine transporter genes that affects reporter gene expression. Neurosci Lett 334:206-210.
44. Ioannidis JPA, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG. 2001. Replication validity of genetic association studies. Nat Genet 29:306-309.
45. Jacobsen LK, Staley JK, Zoghbi SS, Seibyl JP, Kosten TR, Innis RB, et al. 2000. Prediction of dopamine transporter binding availability by genotype: A preliminary report. Am J Psychiatry 157:1700-1703.
46. *Jiang SD, Xin RN, Qian YP, Lin SC, Tang GM, Wang DY, et al. 1999. The relationship between attention2deficit hyperactivity disorder and dopamine transporter 1 gene. Chin J Nerv Ment Dis 25:355-357 (in Chinese).
47. Kang AM, Palmatier MA, Kidd KK. 1999. Global variation of a 40-bp VNTR in the 39-untranslated region of the dopamine transporter gene (SLC6A3). Biol Psychiatry 46:151-160.
48. *Kim YS, Leventhal BL, Kimd SJ, Kime BN, Cheon KA, Yoo HJ, et al. 2005. Family-based association study of DAT1 and DRD4 polymorphism in Korean children with ADHD. Neurosci Lett 390:176-181.
49. *Kirley A, Hawi Z, Daly G, McCarron M, Mullins C, Millar N, et al. 2002. Dopaminergic system genes in ADHD: Toward a biological hypothesis. Neuropsychopharmacology 27:607-619.
50. Krause KH, Dresesl SH, Krause J, Kung HF, Tatsch K. 2000. Increased striatal dopamine transporter in adult patients with attention deficit hyperactivity disorder: Effects of methylphenidate as measured by single photon emission computed tomography. Neurosci Lett 285:107-110.
51. Krause KH, Dresesl SH, Krause J, la Fougere C, Ackenheil M. 2003. The dopamine transporter and neuroimaging in attention deficit hyperactivity disorder. Neurosci Biobehav Rev 27:605-613.
52. *Kustanovich V, Ishii J, Crawford L, Yang M, McGough JJ, McCracken JT, et al. 2004. Transmission disequilibrium testing of dopamine-related candidate gene polymorphisms in ADHD: Confirmation of association of ADHD with DRD4 and DRD5. Mol Psychiatry 9:711-717.
53. *Langley K, Turic D, Peirce TR, Mills S, Van Den Bree MB, Owen MJ, et al. 2005. No support for association between the dopamine transporter (DAT1) gene and ADHD. Am J Med Genet Part B 139B:7-10.
54. Levy F. 1991. The dopamine theory of attention deficit hyperactivity disorder (ADHD). Aust N Z J Psychiatry 25:277-283.
55. Levy F, Hay DA, McStephen M, Wood C, Waldman I. 1997. Attention-deficit hyperactivity disorder: A category or a continuum? Genetic analysis of a large-scale twin study. J Am Acad Child Adol Psychiatry 36:737-744.
56. Lewis DA, Melchitzky DS, Sesack SR, Whitehead RE, Auh S, Sampson A. 2001. Dopamine transporter immunoreactivity in monkey cerebral cortex: Regional, laminar, and ultrastructural localization. J Comp Neurol 432:119-136.
57. Li LB, Chen N, Ramamoorthy S, Chi L, Cui XN, Wang LC, et al. 2004. The role of N-glycosylation in function and surface trafficking of the human dopamine transporter. J Biol Chem 279:21012-21020.
58. Loo SK, Fisher SE, Francks C, Ogdie MN, MacPhie IL, Yang M, et al. 2004. Genome-wide scan of reading ability in affected sibling pairs with attention-deficit/hyperactivity disorder: Unique and shared genetic effects. Mol Psychiatry 9:485-493.
59. *Lunetta KL, Faraone SV, Biederman J, Laird NM. 2000. Family-based tests of association and linkage that use unaffected sibs, covariates, and interactions. Am J Hum Genet 66:605-614.
60. Madras BK, Miller GM, Fischman AJ. 2002. The dopamine transporter: Relevance to attention deficit hyperactivity disorder (ADHD). Behavior Brain Res 130:57-63.
61. *Maher BS, Marazita ML, Ferrell RE, Vanyukov MM. 2002. Dopamine system genes and attention deficit hyperactivity disorder: A meta-analysis. Psychiatr Genet 12:207-215.
62. Martinez D, Gelernter J, Abi-Dargham A, van Dyck CH, Kegeles L, Innis RB, et al. 2001. The variable number of tandem repeats polymorphism of the dopamine transporter gene is not associated with significant change in dopamine transporter phenotype in humans. Neuropsychopharmacology 24:553-560.
63. Michaelhaugh SK, Fiskerstrand C, Lovejoy E, Bannon MJ, Quinn JP. 2001. The dopamine transporter gene (SLC6A3) variable number of tandem repeats domain enhances transcription in dopamine neurons. J Neurochem 79:1033-1038.
64. Mill J, Asherson P, Browes C, D'Souza U, Craig I. 2002. Expression of the dopamine transporter gene is regulated by the 3′-UTR VNTR: Evidence from brain and lymphocytes using quantitative RT-PCR. Am J Med Genet 114:975-979.
65. Mill J, Asherson P, Craig I, D'Souza UM. 2005. Transient expression analysis of allelic variants of a VNTR in the dopamine transporter gene (DAT1). BMC Genet 6:3.
66. Miller GM, Madras BK. 2002. Polymorphisms in the 3′-untranslated region of human and monkey dopamine transporter genes affect reporter gene expression. Mol Psychiatry 7:44-55.
67. Mitchell RJ, Howlett S, Earl L, White NG, Mccomb J, Schanfield MS, et al. 2000. Distribution of the 3′ VNTR polymorphism in the human dopamine transporter gene in world population. Human Biol 72:295-304.
68. Mosteller F, Colditz GA. 1996. Understanding research synthesis (meta-analysis). Annu Rev Public Health 17:1-23.
69. Muglia P, Jain U, Inkster B, Kennedy JL. 2002. A quantitative trait locus analysis analysis of the dopamine transport gene in adults with ADHD. Neuropsychopharmacology 27:655-662.
70. Nadder TS, Silberg JL, Eaves LJ, Maes HH, Meyer JM. 1998. Genetic effects on ADHD symptomatology in 7- to 13-Year-Old Twins: Results from a Telephone Survey. Behavior Genet 28:83-99.
71. Nakamura Y, Koyama K, Matsushima M. 1998. VNTR (variable number of tandemrepeat) sequences as transcriptional, translational, or functional regulators. J Hum Genet 43:149-152.
72. Palmer CG, Bailey JN, Ramsey C, Cantwell D, Sinsheimer JS, Del'Homme M, et al. 1999. No evidence of linkage or linkage disequilibrium between DAT1 and attention deficit hyperactivity disorder in a large sample. Psychiatr Genet 9:157-160.
73. Purper-Ouakila P, Wohla M, Mourena MC, Verpillat P, Ade J, Gorwood P. 2005. Meta-analysis of family-based association studies between the dopamine transporter gene and attention deficit hyperactivity disorder. Psychiatr Genet 15:53-59.
74. Qian Q, Wang Y, Li J, Yang L, Wang B, Zhou R. 2003. Association studies of dopamine D4 receptor gene and dopamine transporter gene polymorphisms in Han Chinese patients with attention deficit hyperactivity disorder. Beijing Da Xue Xue Bao 35:412-418 (in Chinese).
75. *Qian QJ, Wang YF, Zhou RL, Yang L, Faraone SV. 2004. Family-based and case-control association studies of DRD4 and DAT1 polymorphisms in Chinese attention deficit hyperactivity disorder patients suggest long repeats contribute to genetic risk for the disorder. Am J Med Genet Part B 128B:84-89.
76. Rice JP. 1997. The role of meta-analysis in linkage studies of complex traits. Am J Med Genet 74:112-114.
77. *Roman T, Schmitz M, Polanczyk G, Eizirik M, Rohde LA, Hutz MH. 2001. Attention-deficit hyperactivity disorder: A study of association with both the dopamine transporter gene and the dopamine D4 receptor gene. Am J Med Genet 105:471-478.
78. Schaid DJ, Sommer SS. 1994. Comparison of statistics for candidate-gene association studies using cases and parents. Am J Hum Genet 55:402-409.
79. *Simseka M, Al-Sharbatib M, Al-Adawib S, Gangulyc SS, Lawatia K. 2005. Association of the risk allele of dopamine transporter gene (DAT1*10) in Omani male children with attention-deficit hyperactivity disorder. Clin Biochem 38:739-742.
80. Sorrentino E, Volpicelli F, Eyman M, Greco D, Viggiano D, di Porzio U, et al. 2003. Altered midbrain dopaminergic neurotransmission during development in an animal model of ADHD. Neurosci Biobehav Rev 27:661-699.
81. *Swanson JM, Flodman P, Kennedy J, Spence MA, Moyzis R, Schuck S, et al. 2000. Dopamine genes and ADHD. Neurosci Behavior Rev 24:21-25.
82. Tannock R. 1998. Attention deficit hyperactivity disorder: Advances in cognitive, neurobiological, and genetic research. J Child Psychol Psychiatr 39:65-99.
83. Todd RD. 2000. Genetics of attention deficit/hyperactivity disorder: Are we ready for molecular genetic studies? Am J Med Genet 96:241-243.
84. Todd RD, Botteron KN. 2001. Is attention-deficit/hyperactivity disorder an energy deficiency syndrome? Biol Psychiatry 50:151-158.
85. *Todd RD, Jong YJ, Lobos EA, Reich W, Heath AC, Neuman RJ. 2001. No association of the dopamine transporter gene 3_ VNTR polymorphism with ADHD subtypes in a population sample of twins. Am J Med Genet 105:745-748.
86. Vandenbergh DJ, Persico AM, Hawkins AL, Griffin CA, Li X, Jabs EW, et al. 1992. Human dopamine transporter gene (DAT1) maps to chromosome 5p15.3 and displays a VNTR. Genomics 14:1104-1106.
87. Vandenbergh DJ, Thompson MD, Cook EH, Bendahhou E, Nguyen T, Krasowski MD, et al. 2000. Human dopamine transporter gene: Coding region conservation among normal, Tourette's disorder, alcohol dependence and attention-deficit hyperactivity disorder populations. Mol Psychiatry 5:283-292.
88. VanNess SH, Owens MJ, Kilts CD. 2005. The variable number of tandem repeats element in DAT1 regulates in vitro dopamine transporter density. BMC Genet 6:55-65.
89. Viggiano D, Grammatikopoulos G, Sadile AG. 2002. A morphometric evidence for a hyperfunctioning mesolimbic system in an animal model of ADHD. Behavior Brain Res 130:181-189.
90. Vilar J, Piaggio G, Carroli G, Donner A. 1997. Factor affecting the comparability of meta-analyses and largest trials results in perinatology. J Clin Epidemiol 50:997-1002.
91. Volkow ND, Wang GJ, Fowler JS, Gatley SJ, Logan J, Ding YS, et al. 1998. Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. Am J Psychiatry 155:1325-1331.
92. *Waldman ID, Rowe DC, Abramowitz A, Kozel ST, Mohr JH, Sherman SL, et al. 1998. Association and linkage of the dopamine transporter gene and attention-deficit hyperactivity disorder in children: Heterogeneity owing to diagnostic subtype and severity. Am J Hum Genet 63:1767-1776.
93. *Wang ZH, Wang YP, Yao KN, Yang YF, Liu L. 2004. Survey the association between dopamine transporter gene polymorphism and attention def icit hyperactivity disorder. CJCHC 12:289-292 (in Chinese).
94. Willcutt EG, Pennington BF, DeFries JC. 2000. Twin study of the etiology of comorbidity between reading disability and attention-deficit/hyperactivity disorder. Am J Med Genet 96:293-301.
95. Xu M, Moratalla R, Gold LH, Hiroi N, Koob GF, Graybiel AM, et al. 1994. Dopamine D1 receptor mutant mice are deficient in striatal expression of dynorphin and in dopamine-mediated behavioral responses. Cell 79:729-742.