Molecular Biology Reports

, Volume 39, Issue 12, pp 11081–11086 | Cite as

Association study between the dopamine-related candidate gene polymorphisms and ADHD among Saudi Arabia population via PCR technique

  • Adel E. El-TarrasEmail author
  • Adnan A. Alsulaimani
  • Nabil S. Awad
  • Nahla Mitwaly
  • Manal M. Said
  • Ayman M. Sabry


Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood behavioral disorders characterized by inattention, hyperactivity and impulsivity. In Saudi Arabia the prevalence of combined ADHD is 16.4 %. ADHD etiology is not clear and not completely understood. There are several evidences for involvement of dopaminergic, serotonergic and noradrenergic neurotransmitter systems in the pathogenesis of ADHD. Monoamine Oxidase A (MAOA) is involved in the degradation of all three of these neurotransmitters. Dopamine Transporter 1 (DAT1) plays an important role in controlling blood levels of dopamine. The aim of the present study is to investigate the association between ADHD and polymorphisms of MAOA 30 bp-promoter VNTR and DAT1 40 bp 3′ UTRVNTR in Saudi population. PCR technique was employed to detect polymorphisms of MAOA and DAT1 genes in a sample of 120 ADHD subjects and 160 controls. Alleles and genotypes frequencies for both of MAOA and DAT1 polymorphisms were compared among ADHD subjects against controls. Association between ADHD and alleles as well as genotypes for each studied polymorphisms was tested by odds ratio (OR) test and the magnitude of this association was estimated by 95 % confidence interval (95 % CI). A significant association was found between two MAOA genotypes 3/4 and 3/2 with ADHD (P < 0.01, OR = 3, 4.9) as a risk effect. No significant association was found with MAOA alleles. Among DAT1 polymorphisms two alleles (7 and 11 repeats) (P < 0.01, OR = 2.5 and 3.3) as well as two genotypes (11/11 and 11/7) (P < 0.01, OR = 4, 3) showed significant association with ADHD as a risk effect. On the contrary, 9 and 10 repeats revealed significant association as a protective effect as well as 10/10 and 10/9 genotypes. These findings support the hypothesis that some of the MAOA and DAT1 polymorphisms have a causative role in the development of ADHD in the Saudi population. Another polymorphism did not give rise to support this hypothesis. This is the first report investigated the association between MAOA and DAT1 polymorphism at molecular level in Saudi Arabia population as well as Arab world. Therefore further studies are needed to generalize obtained results at Saudi Arabia.


ADHD Association Polymorphisms MAOA 30 bp-promoter VNTR DAT1 40 bp 3′ UTRVNTR Saudi Arabia 


  1. 1.
    American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, Fourth edition, Text revision. American Psychiatric Association, Washington, DCGoogle Scholar
  2. 2.
    Anderson JS, Williams S, McGee R, Silva PA (1987) DSM-III-R disorders in preadolescent children: prevalence in a large sample from the general population. Arch Gen Psychiatry 44(1):69–76PubMedCrossRefGoogle Scholar
  3. 3.
    Skounti M, Philalithis A, Galanakis E (2007) Variations in prevalence of attention deficit hyperactivity disorder worldwide. Eur J Pediatr 166(2):117–123PubMedCrossRefGoogle Scholar
  4. 4.
    Al Hamed J, Taha A, Sabra A, Bella H (2008) Attention deficit hyperactivity disorder (ADHD) among male primary school children in Dammam, Saudi Arabia: prevalence and associated factors. J Egypt Public Health Assoc 83(3–4):165–182PubMedGoogle Scholar
  5. 5.
    Farah LG, Fayyad JA, Eapen V, Cassir Y, Salamoun MM, Tabet CC, Mneimneh ZN, Karam EG (2009) ADHD in the Arab world a review of epidemiologic studies. J Atten Disord 13(3):211–222PubMedCrossRefGoogle Scholar
  6. 6.
    Lawson C, Turic D, Langley K, Pay M, Govan F, Norton N, Hamshere L, Owen J, O’Donovan C, Thapar A (2003) Association analysis of monoamine oxidase A and attention deficit hyperactivity disorder. Am J Med Genet 116:84–89CrossRefGoogle Scholar
  7. 7.
    Khan SA, Faraone SV (2005) The genetics of ADHD: a literature review of 2005. Curr Psychiatry Rep 8(5):393–397CrossRefGoogle Scholar
  8. 8.
    Boomsma DI, Saviouk V, Hottenga J, Distel M, de Moor M, Vink JM, Geels LM, van Beek JH, Bartels M, de Geus EC, Willemsen G (2010) Genetic epidemiology of attention deficit hyperactivity disorder (ADHD Index) in adults. PLoS ONE 5(5):e10621. doi: 10.1371/journal.pone.0010621 PubMedCrossRefGoogle Scholar
  9. 9.
    Jiang S, Xin R, Wu X, Lin S, Qian Y, Ren D, Tang G, Wang D (2000) Association between attention deficit hyperactivity disorder and the DXS7 locus. Am J Med Genet 96:289–292PubMedCrossRefGoogle Scholar
  10. 10.
    Volkow ND, Wang GJ, Fowler JS, Gatley SJ, Logan J, Ding YS (1998) Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. Am J Psychiatry 155:1325–1331PubMedGoogle Scholar
  11. 11.
    Jaber M, Jones S, Giros B, Caron MG (1997) The dopamine transporter: a crucial component regulating dopamine transmission. Mov Disord 12:629–633PubMedCrossRefGoogle Scholar
  12. 12.
    Waldman ID, Gizer IR (2006) The genetics of attention deficit hyperactivity disorder. Clin Psychol Rev 6:396–432CrossRefGoogle Scholar
  13. 13.
    Mick E, Faraone SV (2008) Genetics of attention deficit hyper-activity disorder. Child Adolesc Psychiatr Clin N Am 17:261–284PubMedCrossRefGoogle Scholar
  14. 14.
    Sevinc E, Erdal M, Sengul C, Cakaloz B, Ergundu TG, Herken H (2010) Association of adult attention deficit hyperactivity disorder with dopamine transporter gene, dopamine D3 receptor, and dopamine D4 receptor gene polymorphisms. Bull Clin Psychopharmacol 20:196–203Google Scholar
  15. 15.
    Conners CK (1998) Rating scales in attention-deficit/hyperactivity disorder: use in assessment and treatment monitoring. J Clin Psychiatry 59(Suppl 7):24–30PubMedGoogle Scholar
  16. 16.
    Achenbach TM, Edelbrock CS (1981) Behavioral problems and competencies reported by parents of normal and disturbed children aged four through sixteen. Monogr Soc Res Child Dev 46:1–82PubMedCrossRefGoogle Scholar
  17. 17.
    Karcher SJ (1995) Polymerase chain reaction. In: Molecular biology, a project approach, 1st edn, Academic Press, San Diego, p 79–110Google Scholar
  18. 18.
    Manor I, Tyano S, Me E, Eisenberg J, Bachner-Melman R, Kotler M, Ebstein RP (2002) Family-based and association studies of monoamine oxidase A and attention deficit hyperactivity disorder (ADHD): preferential transmission of the long promoter region repeat and its association with impaired performance on a continuous performance test (TOVA). Mol Psychiatry 7:626–632PubMedCrossRefGoogle Scholar
  19. 19.
    Wang Y, Wang Z, Yao K, Tanaka K, Yang Y, Shirakawa O, Maeda K (2007) Lack of association between the dopamine transporter gene 3′VNTR polymorphism and attention deficit hyperactivity disorder in Chinese Han children: case-control and family-based studies. Kobe J Med Sci 53(6):327–333Google Scholar
  20. 20.
    Simsek M, Al-Sharbati M, Al-Adawi S, Lawatia K (2006) The VNTR polymorphism in the human dopamine transporter gene: improved detection and absence of association of VNTR alleles with attention-deficit hyperactivity disorder. Genet Test 10(1):31–34PubMedCrossRefGoogle Scholar
  21. 21.
    Payton A, Holmes J, Barrett JH, Hever T, Fitzpatrick H, Trumper AL, Harrington R, McGuffin P, O’Donovan M, Owen M, Ollier W, Worthington J, Thapar A (2001) Examining for association between candidate gene polymorphisms in the dopamine pathway and attention-deficit hyperactivity disorder: a family based study. Am J Med Genet 105:464–470PubMedCrossRefGoogle Scholar
  22. 22.
    Qian Q, Wang Y, Zhou R, 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 B Neuropsychiatr Genet 128B(1):84–89PubMedCrossRefGoogle Scholar
  23. 23.
    Scahill L, Schwab-Stone M (2000) Epidemiology of ADHD in school-age children. Child Adolesc Psychiatr Clin N Am 9(3):541–555PubMedGoogle Scholar
  24. 24.
    Li D, Sham PC, Owen MJ, He L (2006) Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD). Hum Mol Genet 15(14):2276–2284PubMedCrossRefGoogle Scholar
  25. 25.
    Smith KM, Daly M, Fischer M, Yiannoutsos CT, Bauer L, Barkley R, Navia BA (2003) Association of the dopamine beta hydroxylase gene with attention deficit hyperactivity disorder: genetic analysis of the Milwaukee longitudinal study. Am J Med Genet B Neuropsychiatr Genet 119B:77–85PubMedCrossRefGoogle Scholar
  26. 26.
    Zhou K, Arcos-Burgos M, Bakker SC, Banaschewski T, Biederman J, Buitelaar J, Castellanos FX, Dempfle A, Doyle A, Ebstein RP, Ekholm J, Forabosco P, Franke B, Freitag C, Friedel S, Gill M, Hebebrand J, Hinney A, Jacob C, Lesch KP, Loo SK, Lopera F, McCracken JT, McGough JJ, Meyer J, Mick E, Miranda A, Muenke M, Mulas F, Nelson SF, Nguyen TT, Oades RD, Ogdie MN, Palacio JD, Pineda D, Reif A, Renner TJ, Roeyers H, Romanos M, Rothenberger A, Schafer H, Sergeant J, Sinke RJ, Smalley SL, Sonuga-Barke E, Steinhausen HC, van der Meulen E, Walitza S, Warnke A, Lewis CM, Faraone SV, Asherson P (2008) Meta-analysis of genome-wide linkage scans of attention deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet 147B(8):1392–1398PubMedCrossRefGoogle Scholar
  27. 27.
    Cook EH, Stein MA, Krasowski MD, Cox NJ, Olkon DM, Keiffer JE (1995) Association of attention deficit disorder and the dopamine transporter gene. Am J Hum Genet 56:993–998PubMedGoogle Scholar
  28. 28.
    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 2:311–313PubMedCrossRefGoogle Scholar
  29. 29.
    Waldman ID, Rowe DC, Abramowitz A, Kozel ST, Mohr JH, Sherman SL (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 63:1767–1776PubMedCrossRefGoogle Scholar
  30. 30.
    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 4:192–196PubMedCrossRefGoogle Scholar
  31. 31.
    Curran S, Mill J, Tahir E, Kent L, Richards S, Gould A, Huckett L, Sharp J, Batten C, Fernando S, Ozbay F, Yazgan Y, Simonoff E, Thompson M, Taylor E, Asherson P (2001) Association study of a dopamine transporter polymorphism and attention deficit hyperactivity disorder in UK and Turkish samples. Mol Psychiatry 6:425–428PubMedCrossRefGoogle Scholar
  32. 32.
    Barr CL, Feng Y, Wigg KG, Schachar R, Tannock R, Roberts W, Malone M, Kennedy JL (2001) 5′-Untranslated region of the dopamine D4 receptor gene and attention-deficit hyperactivity disorder. Am J Med Genet 105:84–90PubMedCrossRefGoogle Scholar
  33. 33.
    Chen CK, Chen SL, Mill J, Huang YS, Lin SK, Curran S, Purcell S, Sham P, Asherson P (2003) The dopamine transporter gene is associated with attention deficit hyperactivity disorder in a Taiwanese sample. Mol Psychiatry 8(4):393–396PubMedCrossRefGoogle Scholar
  34. 34.
    Lim MH, Kim HW, Paik KC, Cho SC, Yoon do Y, Lee HJ (2006) Association of the DAT1 polymorphism with attention deficit hyperactivity disorder (ADHD): a family-based approach. Am J Med Genet B Neuropsychiatr Genet 141:309–311Google Scholar
  35. 35.
    Todd RD, Rasmussen ER, Neumann RJ, Reich W, Hudziak J, Bucholz KK, Madden P, Heath AC (2001) Familiality and heritability of ADHD subtypes in a population sample of female twins. Am J Psychiatry 158:1891–1898PubMedCrossRefGoogle Scholar
  36. 36.
    Maher BS, Marazita ML, Ferrell RE, Vanyukov MM (2002) Dopamine system genes and attention deficit hyperactivity disorder: a meta-analysis. Psychiatr Genet 12:207–215PubMedCrossRefGoogle Scholar
  37. 37.
    Muglia P, Jain U, Kennedy JL (2002) A transmission disequilibrium test of the Ser9 Gly dopamine D3 receptor gene polymorphism/in adult attention deficit hyperactivity disorder. Behav Brain Res 130:91–95PubMedCrossRefGoogle Scholar
  38. 38.
    Kim YS, Leventhal BL, Kim SJ, Kim BN, Cheon KA, Yoo HJ, Kim SJ, Badner J, Cook EH (2005) Family-based association study of DAT1 and DRD4 polymorphism in Korean children with ADHD. Neurosci Lett 390:176–181PubMedCrossRefGoogle Scholar
  39. 39.
    Langley K, Turic D, Peirce TR, Mills S, Van Den Bree MB, Owen MJ, O’Donovan MC, Thapar A (2005) No support for association between the dopamine transporter (DAT1) gene and ADHD. Am J Med Genet B Neuropsychiatr Genet 139:7–10Google Scholar
  40. 40.
    Cheuk DK, Li SY, Wong V (2006) No association between VNTR polymorphisms of dopamine transporter gene and attention deficit hyperactivity disorder in Chinese children. Am J Med Genet B Neuropsychiatr Genet 141:123–125Google Scholar
  41. 41.
    Deborah C, Darko T, Kate L, Helen M, Catherine G, Nadine No, Marian L, Michael J, Michael C, Thapar A (2003) Association analysis of monoamine oxidase A and attention deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet 116B:84–89CrossRefGoogle Scholar
  42. 42.
    Domschke K, Sheehan K, Lowe N, Kirley A, Mullins C, O’sullivan R, Freitag C, Becker T, Conroy J, Fitzgerald M, Gill M, Hawi Z (2005) Association analysis of the monoamine oxidase A and B genes with attention deficit hyperactivity disorder (ADHD) in an Irish sample: preferential transmission of the MAOA 941G allele to affected children. Am J Med Genet B Neuropsychiatr Genet 134B:110–114PubMedCrossRefGoogle Scholar
  43. 43.
    Xu X, Brookes K, Chen CK, Huang Yu 2, Yu Wu, Asherson P (2007) Association study between the monoamine oxidase A gene and attention deficit hyperactivity disorder in Taiwanese samples. BMC Psychiatry 7:10. doi: 10.1186/1471-244X-7-10 PubMedCrossRefGoogle Scholar
  44. 44.
    Brookes K, Xu X, Chen W, Zhou K, Neale B, Lowe N, Anney 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, Gabriëls I, Korn-Lubetzki I, Johansson L, Marco R, Medad S, Minderaa R, Mulas F, Müller 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, Eisenberg J, Kuntsi J, Manor I, McGuffin P, Miranda A, Oades RD, Plomin R, Roeyers H, Rothenberger A, Sergeant J, Steinhausen H-C, Taylor E, Thompson M, Faraone SV, Asherson P (2006) The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes. Mol Psychiatry 11:934–953PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Adel E. El-Tarras
    • 1
    Email author
  • Adnan A. Alsulaimani
    • 2
  • Nabil S. Awad
    • 1
  • Nahla Mitwaly
    • 3
  • Manal M. Said
    • 4
  • Ayman M. Sabry
    • 1
  1. 1.Biotechnology and Genetic Engineering Unit, College of MedicineTaif UniversityTaifKingdom of Saudi Arabia
  2. 2.College of MedicineTaif UniversityTaifKingdom of Saudi Arabia
  3. 3.Department of Psychology, Faculty of EducationTaif UniversityTaifKingdom of Saudi Arabia
  4. 4.Department of Biotechnology, College of ScienceTaif UniversityTaifKingdom of Saudi Arabia

Personalised recommendations