Studying Association 48 bp Polymorphism of DRD4 Gene with Attention Deficit Hyperactivity Disorder in Children from North West of Iran

Hosseinpourefeizi , Mohammadali; mehdizadeh fanid, Leila; Noorazar , Gholamreza; Adampourezare , Mina; Golipour Falahi , Mohammadrezare

Volume 25, Issue 5 (Jul-Aug 2017) JSSU 2017, 25(5): 396-403 | Back to browse issues page

Mendeley

Zotero

RefWorks

Hosseinpourefeizi M, mehdizadeh fanid L, Noorazar G, Adampourezare M, Golipour Falahi M. Studying Association 48 bp Polymorphism of DRD4 Gene with Attention Deficit Hyperactivity Disorder in Children from North West of Iran . JSSU 2017; 25 (5) :396-403
URL: http://jssu.ssu.ac.ir/article-1-4177-en.html

Studying Association 48 bp Polymorphism of DRD4 Gene with Attention Deficit Hyperactivity Disorder in Children from North West of Iran

Mohammadali Hosseinpourefeizi

, Leila Mehdizadeh fanid ^*

, Gholamreza Noorazar

, Mina Adampourezare

, Mohammadrezare Golipour Falahi

Abstract: (5253 Views)

Introduction: Attention deficit hyperactivity disorder (ADHD) is a multifactorial disorder that has defined by hyperactivity, impulsivity and attention deficits. Various neurotransmitters such as dopamine can play a role in its pathophysiology. The aim of this study was to examine the association of two common single nucleotid polymorphisms in DRD₄ gene, a 48 bp VNTR polymorphism, with attention deficit hyperactivity disorder risk among Iranian-Azeri population.
Materials and methods: case–control study was performed on 50 children with attention deficit hyperactivity disorder and 50 healthy ones. Peripheral blood samples were used for Genomic DNA extraction by proteinase K method. The collected data were analyzed through chi-square test (x²), with a significance level of 0.05.
Results: considering the obtained results, there was a significant increase in 4/8 genotype frequency between two groups (p<0.05). Although, there was no significant difference in the allele and genotype frequencies in other genotypes between cases and controls (p>0.05).
Conclusion: Our data confirmed the relationship between polymorphism of DRD4 and ADHD. Further studies with larger population of other groups will be required to explain the relationship between DRD4 polymorphism and the risk of ADHD

Keywords: Key words: ADHD, DRD4 gene, polymorphism, molecular marker

Full-Text [PDF 742 kb] (1478 Downloads)

Type of Study: Original article | Subject: Genetics
Received: 2017/04/24 | Accepted: 2017/07/29 | Published: 2017/10/3

References

1. Nair J, Ehimare U, Beitman B, Nair S, Lavin A. Clinical review: evidence-based diagnosis and treatment of ADHD in children. Missouri medicine 2006; 103(6): 617-21.

2. Rapport MD. Attention deficit disorder with hyperactivity. Behavior therapy with children and adolescents. A clinical approach 1987; 325-367.

3. Biederman J, Spencer T. Attention deficit/hyperactivity disorder (ADHD) as a noradrenergic disorder. Biological psychiatry 1999; 46(9): 1234-42.

4. Swanson JM, Kinsbourne M, Nigg J, Lanphear B, Stefanatos GA, Volkow N, et al. Etiologic subtypes of attention-deficit/hyperactivity disorder: brain imaging, molecular genetic and environmental factors and the dopamine hypothesis. Neuropsychol Rev 2007; 17(1): 39-59.

5. Gizer IR, Ficks C, and Waldman ID. Candidate gene studies of ADHD: a meta-analytic review. Hum Genet 2009; 126(1): 51–90.

6. Goldman-Rakic PS, Castner SA, Svensson TH, Siever LJ, Williams GV. Targeting the dopamine D1 receptor in schizophrenia: insights for cognitive dysfunction. Psychopharmacology 2004; 174: 3-16.

7. Obollo MA, Montiel S. Attention and the executive function. Rev Neural 2006; 42(2): 3-7.

8. Matsumoto M, Hidaka K, Tada S, Tasaki Y, Yamaguchi T. Full length cDNA cloning and distribution of human dopamine D4 receptor. Brain res molecular brain res 1995; 29(1): 157-62.

9. Faraone SV, Perlis RH, Doyle AE. Molecular genetics of attentiondeﬁcit/hyperactivity disorder. Biol Psychiatry 2005; 57(11): 1313-23.

10. Staller JA, Faraone SV. Targeting the dopamine system in the treatment of attention-deﬁcit/hyperactivity disorder. Expert Rev Neurother 2007; 7(4): 351-362.

11. Forssberg H, Fernell E, Waters S. Altered pattern of brain dopamine synthesis in male adolescents with attention deﬁcit hyperactivity disorder. Behav Brain Funct 2006; 2(1): 40.

12. Li D, Sham PC, Owen MJ. Meta-analysis shows signiﬁcant association between dopamine system genes and attention deﬁcit hyperactivity disorder (ADHD). Hum Molecular Genet 2006; 15: 2276-84.

13. Asghari V, Sanyal S, Buchwaldt S. Modulation of intracellular cyclic AMP levels by different human dopamine D4 receptor variants. J Neurochem 1995; 65(3): 1157-65.

14. Rohde LA, Halpern R. Recentadvences on attention deficit/hyperactivity disorder. Journal de Pediatria, 80 Suppl 2004; (80)2: 61-70.

15. Oak JN, Oldenhof J, Van Tol HH. The dopamine D(4) receptor: One decade of research. Eur J Pharmacol 2000; 405(1): 303-327.

16. Holmes J, Payton A, Barrett JH. A family-based and case-control association study of the dopamine D4 receptor gene and dopamine transporter gene in attention deficit hyperactivity disorder. Mol Psychiatry 2000; 5(5): 523-530.

17. Tahir E, Yazgan Y, Cirakoglu B. Association and linkage of DRD4 and DRD5 with attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children. Mol Psychiatry 2000; 5(4): 396–404.

18. Roman T, Schmitz M, Polanczyk G. Attention-deficit hyperactivity disorder: A study of association with both the dopamine transporter gene and the dopamine D4 receptor gene. Am J Med Genet 2001; 105(5): 471–78.

19. Castellanos FX, Lau E, Tayebi N, Lee P, Long RE, Giedd JN. Lack of an association between a dopamine-4 receptor polymorphism and attention- deficit/hyperactivity disorder: Genetic and brain morphometric analyses. Mol Psychiatry1998; 3(5): 431–34.

20. Marino C, Giorda R, Vanzin L, Molteni M, Lorusso M. L, Nobile M, et al. No evidence for association and linkage disequilibrium between dyslexia and markers of four dopamine-related genes. Eur Child Adolesc Psychiatry 2003; 12(4): 198–202.

21. Johansson S, Halleland H, Halmّy A, Jcobsen KK, Landaas ET, Dramsdahl M, ET AL. Genetic analyses of dopamine related genes in adult ADHD patients suggest an association with the DRD5-microsatellite repeat but not with DRD4 or SLC6A3 VNTRs. Am J Med Genet B Neuropsychiatr Genet 2008;147B(8): 1470–75.

22. Swanson JM, Kinsbourne M, Nigg J, Lanphear B, Stefanatos GA, Volkow N, et al. .Etiologic subtypes of attention-deficit/hyperactivity disorder: brain imaging, molecular genetic and environmental factors and the dopamine hypothesis. Neuropsychol Rev 2007; 17(1): 39-59.

23. Ji HS, Paik KC, Park WS, Lim MH. No association between the response to methylphenidate and DRD4 gene polymorphism in Korean attention deficit hyperactivity disorder: A case control study. ClinPsychopharmacolNeurosci 2013; 11(1): 13-7.

25. Guney E, Iseri E, Ergun SG, Percin EF, Ergun MA, Yalcin O, et al. The Correlation of Attention Deficit Hyperactivity Disorder withDRD4 Gene Polymorphism in Turkey. Int J Hum Genet 2013; 13(3): 145-52.

26. Turic D, Swanson J, Sonuga-Barke E. DRD4 and DAT1in ADHD: Functionalneurobiology to pharmacogenetics. PharmgenomicsPers Med 2010; 3: 61-78.

27. Bidwell LC, Willcutt EG, McQueen MB, DeFries JC, Olson RK, Smith SD, et al. A family based association study of DRD4, DAT1, and 5HTT and continuous traits of attention-deficit hyperactivity disorder. Behav Genet 2011; 41:165-174.

28. Grizenko N, Fortier ME, Zadorozny C, Thakur G, Schmitz N, Duval R, Joober R. Maternal stress during pregnancy, ADHD symptomatology in children and genotype: Gene-environment ‎nteraction. J Can Acad Child Adolesc Psychiatry2012; 21(1): 9-15.

29. Tabatabaei S.M, Amiri Sh, Faghfouri S, Noorazar Gh, AbdollahiFakhim Sh, Fakhari A. DRD4 Gene Polymorphisms as a Risk Factor for Children with Attention Deficit Hyperactivity Disorder in Iranian Population. International Scholarly Research Notices. 2017; 2494537- 5

30. Qian Q, Wang Y, Zhou R, Yang L, Faraone SV .Familybasedand case-control association studies of DRD4 andDAT1 polymorphisms in Chinese attention deficithyperactivity disorder patients suggest long repeatscontribute to genetic risk for the disorder. Am J MedGenet B Neuropsychiatr Genet2004; 128B(1): 84–89.

31. Faraone SV, Biederman J, Weiffenbach B, Keith T, Chu MP, Weaver A, et al . Dopamine D4 gene 7-repeat allele andattention deficit hyperactivity disorder. Am J Psychiatry 1999;156(5): 768–770.

32. Holmes J, Payton A, Barrett JH, Hever T, Fitzpatrick H,Trumper AL, et al . A family-basedand case-control association study of the dopamine D4receptor gene and dopamine transporter gene in attentiondeficit hyperactivity disorder. Mol Psychiatry 2000; 5(5): 523–530.

33. Curran S, Mill J, Sham P, Rijsdijk F, Marusic K, Taylor E,Asherson P . QTL association analysis of theDRD4 exon 3 VNTR polymorphism in a populationsample of children screened with a parent rating scalefor ADHD symptoms. Am J Med Genet 2001;105(4): 387–393.

34. Brookes KJ, Xu X, Chen CK, Huang YS, Wu YY, AshersonP .No evidence for the association of DRD4 withADHD in a Taiwanese population within-family study.BMC Med Genet 2005; 6: 31.

35. Kim YS, Leventhal BL, Kim SJ, Kim BN, Cheon KA, YooHJ, et al. Family-basedassociation study of DAT1 and DRD4 polymorphismin Korean children with ADHD. NeurosciLett 2005; 390(3):176–181.

36. Leung PW, Lee CC, Hung SF, Ho TP, Tang CP, Kwong SL, et al. Dopaminereceptor D4 (DRD4) gene in Han Chinese children withattention deficit/hyperactivity disorder (ADHD): Increased prevalence of the 2-repeat allele. Am J MedGenet (Neuropsychiatry Genet) 2005; 133(1): 54-56.