Polymorphism of dopamine transporter gene 3'-UTR VNTR in Iranian Azeri Turkish patients with ADHD

Abdi, Adel; Zeinalzadeh, Narges; Mehdizadeh Fanid, Leila; Khalilinejad, Nava

doi:10.22038/ijp.2022.59297.4621

Polymorphism of dopamine transporter gene 3'-UTR VNTR in Iranian Azeri Turkish patients with ADHD

Document Type : original article

Authors

Adel Abdi ¹

Narges Zeinalzadeh ²

Leila Mehdizadeh Fanid ³

Nava Khalilinejad ⁴

¹ Department of Animal Sciences, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.

² Assistant professor of Molecular Genetics, Department of Animal Sciences, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.

³ Assistant professor of Neuroscience, Division of Cognitive Neuroscience, Department of Psychology, Faculty of Education and Psychology, University of Tabriz, Tabriz, Iran.

⁴ Department of Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran.

10.22038/ijp.2022.59297.4621

Abstract

Background: Attention Deficit Hyperactivity Disorder (ADHD) is the most common neurobehavioral disorder among children, which several studies have indicated the role of genetic factors in its development. Dopamine transporter gene (DAT1) is one of the candidate genes and a 40-bp variable number of tandem repeat (VNTR) in 3'-UTR of the gene is reported to have a role in ADHD. Here we examined the association between DAT1 VNTR and ADHD susceptibility among Iranian Azeri Turkish children.
Methods: The study included 202 patients and 143 controls aged 6-12 years. ADHD children were diagnosed according to DSM-IV and "conners scale" and DAT1 3'-UTR VNTR was genotyped by PCR technique.
Results: The genotypes and allelic distribution of the DAT1 3'-UTR VNTR were not significantly different between the case and control groups (p>0.05) but a significant difference was found in allelic frequencies when the analysis was confined to females (p=0.029).
Conclusion: Our results do not support the role of 10 or 9-repeat alleles as risk alleles in the studied subjects but an association was found between 11-repeat allele and the susceptibility to ADHD in females.

Keywords

Attention deficit hyperactivity disorder

ADHD

DAT1

SLC6A3

3' -UTR VNTR

Polanczyk GV, Willcutt EG, Salum GA, Kieling C, Rohde LA. ADHD prevalence estimates across three decades: an updated systematic review and meta-regression analysis. Int J Epidemiol. 2014; 43(2):434-442.
Simon V, Czobor P, Bálint S, Mészáros A, Bitter I. Prevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis. Br J Psychiatry. 2009; 194(3):204-211.
Association AP. Diagnostic and statistical manual of mental disorders (DSM-5®): American Psychiatric Pub; 2013.
Shooshtary MH, Chimeh N, Najafi M, Mohamadi MR, Yousefi-Nouraie R, Rahimi-Mvaghar A. The prevalence of attention deficit hyperactivity disorder in Iran: A systematic review. Iran J Psychiatry. 2010; 5(3):88.
Faraone SV, Larsson H. Genetics of attention deficit hyperactivity disorder. Mol Psychiatry. 2019; 24(4):562-575.
Faltraco F, Palm D, Uzoni A, Borchert L, Simon F, Tucha O, et al. Dopamine adjusts the circadian gene expression of Per2 and Per3 in human dermal fibroblasts from ADHD patients. J Neural Transm (Vienna). 2021; 128(7):1135-1145.
Shang C-Y, Lin H-Y, Gau SS-F. Effects of the dopamine transporter gene on striatal functional connectivity in youths with attention-deficit/hyperactivity disorder. Psychol Med. 2021; 51(5):835-845.
Faraone SV. The pharmacology of amphetamine and methylphenidate: relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities. Neurosci Biobehav Rev. 2018; 87:255-270.
Yang B, Chan RC, Jing J, Li T, Sham P, Chen RY. 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. Am J Med Genet B Neuropsychiatr Genet. 2007; 144(4):541-550.
Bonvicini C, Faraone S, Scassellati C. Attention-deficit hyperactivity disorder in adults: a systematic review and meta-analysis of genetic, pharmacogenetic and biochemical studies. Mol Psychiatry. 2016; 21(7):872-884.
Bieliński M, Jaracz M, Lesiewska N, Tomaszewska M, Sikora M, Junik R, et al. Association between COMT Val158Met and DAT1 polymorphisms and depressive symptoms in the obese population. Neuropsychiatr Dis Treat. 2017; 18(13):2221-2229.
Li L, Bao Y, He S, Wang G, Guan Y, Ma D, et al. The association between genetic variants in the dopaminergic system and posttraumatic stress disorder: a meta-analysis. Medicine (Baltimore). 2016; 95(11).
Taylor S. Molecular genetics of obsessive–compulsive disorder: a comprehensive meta-analysis of genetic association studies. Mol Psychiatry. 2013; 18(7):799-805.
Cook Jr EH, Stein MA, Krasowski MD, Cox NJ, Olkon DM, Kieffer JE, et al. Association of attention-deficit disorder and the dopamine transporter gene. Am J Hum Genet. 1995; 56(4):993.
Banoei M, Majidizadeh T, Shirazi E, Moghimi N, Ghadiri M, Najmabadi H, et al. No association between the DAT1 10‐repeat allele and ADHD in the Iranian population. Am J Med Genet B Neuropsychiatr Genet. 2008; 147(1):110-111.
El-Tarras AE, Alsulaimani AA, Awad NS, Mitwaly N, Said MM, Sabry AM. Association study between the dopamine-related candidate gene polymorphisms and ADHD among Saudi Arabia population via PCR technique. Mol Biol Rep. 2012; 39(12):11081-11086.
Qian Q, Wang Y, Zhou R, Yang L, Faraone SV. 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. 2004; 128(1):84-89.
Wohl M, Boni C, Asch M, Cortese S, Orejarena S, Mouren M, et al. Lack of association of the dopamine transporter gene in a French ADHD sample. Am J Med Genet B Neuropsychiatr Genet. 2008; 147(8):1509-1510.
Kim YS, Leventhal BL, Kim S-J, Kim B-N, Cheon K-A, Yoo H-J, et al. Family-based association study of DAT1 and DRD4 polymorphism in Korean children with ADHD. Neurosci Lett. 2005; 390(3):176-181.
Wiguna T, Ismail RI, Winarsih NS, Kaligis F, Hapsari A, Budiyanti L, et al. Dopamine transporter gene polymorphism in children with ADHD: a pilot study in Indonesian samples. Asian J Psychiatr. 2017; 29:35-38.
Asherson P, Brookes K, Franke B, Chen W, Gill M, Ebstein RP, et al. Confirmation that a specific haplotype of the dopamine transporter gene is associated with combined-type ADHD. Am J Psychiatry. 2007; 164(4):674-677.
Grünblatt E, Werling AM, Roth A, Romanos M, Walitza S. Association study and a systematic meta-analysis of the VNTR polymorphism in the 3′-UTR of dopamine transporter gene and attention-deficit hyperactivity disorder. J Neural Transm. 2019; 126(4):517-529.
Miller G, Madras B. Polymorphisms in the 3′-untranslated regions of human and monkey dopamine transporter genes affect reporter gene expression. Mol Psychiatry. 2002; 7(1):44-55.
Kanno K, Ishiura S. The androgen receptor facilitates inhibition of human dopamine transporter (DAT1) reporter gene expression by HESR1 and HESR2 via the variable number of tandem repeats. Neurosci Lett. 2012; 525(1); 54-59.