Dopamine transporter 1 (DAT1) rs40184 single nucleotide polymorphism is not associated with the Malaysian major depressive disorder subjects
Major depressive disorder (MDD) is a serious mental illness with a multifactorial aetiology that was shown to influence behaviour and affect cognition. Previous research has favoured the involvement of dopamine in the aetiology of the disorder, and since one of the critical regulators of the dopamine levels and activity in the brain is DAT1, the present study investigated the association of a single nucleotide polymorphism in the DAT1 gene (rs40184) and MDD in the Malaysian population. A total of 300 cases and 300 matched controls were recruited from four Klang valley hospitals and were screened for DAT1 rs40184 using high resolution melting assays. The allele and genotype frequencies were analysed by using Chi-square. Hardy Weinberg equilibrium for the distribution of alleles and genotypes was tested by using Chi-square. Determination of the association between rs40184 and MDD was achieved by conditional logistic regression using SPSS. In the present study, no significant association was obtained between DAT1 and MDD in the Malaysian population.
Aldoghachi AF, Tor YS, Redzun SZ, Lokman KA, Razaq NA, Shahbudin AF, et al. Screening of brain-derived neurotrophic factor (BDNF) single nucleotide polymorphisms and plasma BDNF levels among Malaysian major depressive disorder patients. PloS One. 2019;14(1):e0211241. https://doi.org/10.1371/journal.pone.0211241
Bonhomme N, Esposito E. Involvement of serotonin and dopamine in the mechanism of action of novel antidepressant drugs: a review. J Clin Psychopharmacol. 1998;18(6):447-454. https://www.ncbi.nlm.nih.gov/pubmed/9864076
Ciliax BJ, Heilman C, Demchyshyn LL, Pristupa ZB, Ince E, Hersch SM, et al. The dopamine transporter: immunochemical characterization and localization in brain. J Neurosci. 1995;15(3):1714-1723. https://doi.org/10.1523/JNEUROSCI.15-03-01714.1995
Davis C, Loxton NJ, Levitan RD, Kaplan AS, Carter JC, Kennedy JL. ‘Food addiction’ and its association with a dopaminergic multilocus genetic profile. Physiol Behav. 2013;118:63-69. https://doi.org/10.1016/j.physbeh.2013.05.014
Der-Avakian A, Markou A. The neurobiology of anhedonia and other reward-related deficits. Trends Neurosci. 2012;35(1):68-77. https://doi.org/10.1016/j.tins.2011.11.005
Diagnostic and Statistical Manual of Mental Disorders (DSM-5®). Fifth edition. American Psychiatric Publishing, Incorporated; 2013. pp. 991, ISBN:978-0-89042-554-1.
Donald SR, Robinson MD. The role of dopamine and norepinephrine in depression. Prim Psychiatry. 2007;14(5):21-23.
Dunlop BW, Nemeroff CB. The role of dopamine in the pathophysiology of depression. Arch Gen Psychiatry. 2007;64(3):327-337. https://doi.org/10.1001/archpsyc.64.3.327
Faris A, Yusof HH, Abidin SZ, Habib O, Cheah PS, Stanslas J, et al. Development and validation of high resolution melting assays for high-throughput screening of BDNF rs6265 and DAT1 rs40184. Malay J Med Health Sci. 2018;14(SP1):64-71.
Garnier‐Géré P, Chikhi L. Population Subdivision, Hardy–Weinberg Equilibrium and the Wahlund Effect. In eLS, John Wiley & Sons, Ltd (Ed.). 2013. https://doi.org/10.1002/9780470015902.a0005446.pub3
Gatt JM, Burton KL, Williams LM, Schofield PR. Specific and common genes implicated across major mental disorders: a review of meta-analysis studies. J Psychiatr Res. 2015;60:1-13. https://doi.org/10.1016/j.jpsychires.2014.09.014
Giros BR, el Mestikawy SA, Godinot NA, Zheng KE, Han HO, Yang-Feng TE, et al. Cloning, pharmacological characterization, and chromosome assignment of the human dopamine transporter. Mol Pharmacol. 1992;42(3):383-390. https://www.ncbi.nlm.nih.gov/pubmed/1406597
Haeffel GJ, Getchell M, Koposov RA, Yrigollen CM, De Young CG, Klinteberg BA, et al. Association between polymorphisms in the dopamine transporter gene and depression: evidence for a gene-environment interaction in a sample of juvenile detainees. Psychol Sci. 2008;19(1):62-69. https://doi.org/10.1111/j.1467-9280.2008.02047.x
Hall H, Halldin C, Guilloteau D, Chalon S, Emond P, Besnard JC, et al. Visualization of the dopamine transporter in the human brain postmortem with the new selective ligand [125I]PE2I. Neuroimage. 1999;9(1):108-116. https://doi.org/10.1006/nimg.1998.0366
Hardy GH. Mendelian proportions in a mixed population. Science. 1908;28(706):49-50. https://doi.org/10.1126/science.28.706.49
Huang CC, Lu RB, Shih MC, Yen CH, Huang SY. Association study of the dopamine transporter gene with personality traits and major depressive disorder in the Han Chinese population. Pharmacogenet Genom. 2011;21(2):94-97. https://doi.org/10.1097/FPC.0b013e3283424d94
Joyce PR, Stephenson J, Kennedy MA, Mulder RT, McHugh PC. The presence of both serotonin 1A receptor (HTR1A) and dopamine transporter (DAT1) gene variants increase the risk of borderline personality disorder. Front Genet. 2014;4:313. https://doi.org/10.3389/fgene.2013.00313
Kessler RC, Merikangas KR, Wang PS. Prevalence, comorbidity, and service utilization for mood disorders in the United States at the beginning of the twenty-first century. Annu Rev Clin Psychol. 2007;3:137-158. https://doi.org/10.1146/annurev.clinpsy.3.022806.091444
Levinson DF. The genetics of depression: a review. Biol Psychiatry. 2006;60(2):84-92. https://doi.org/10.1016/j.biopsych.2005.08.024
Lian LH, Loke AC, Zainal NZ, Mohamed Z. Association study of the tryptophan hydroxylase 1 gene with major depressive disorder in three ethnic groups of the Malaysian population. Asian Biomed. 2013;7(1):105-112. https://doi.org/10.5372/1905-7415.0701.156
Mick E, Kim JW, Biederman J, Wozniak J, Wilens T, Spencer T, et al. Family based association study of pediatric bipolar disorder and the dopamine transporter gene (SLC6A3). Am J Med Genet. 2008;147B(7):1182-1185. https://doi.org/10.1002/ajmg.b.30745
Nazree NE, Loke AC, Zainal NZ, & Mohamed Z. Lack of association between TPH2 gene polymorphisms with major depressive disorder in multiethnic Malaysian population. Asia Pac Psychiatry. 2015;7(1):72-77. https://doi.org/10.1111/appy.12118
Otte C, Gold SM, Penninx BW, Pariante CM, Etkin A, Fava M, et al. Major depressive disorder. Nat Rev Dis Primers. 2016;2:16065. https://doi.org/10.1038/nrdp.2016.65
Pattarachotanant N, Sritharathikhun T, Suttirat S, Tencomnao T. Association of C/T polymorphism in intron 14 of the dopamine transporter gene (rs40184) with major depression in a northeastern Thai population. Genet Mol Res. 2010;9(1):565-572. https://doi.org/10.4238/vol9-1gmr757
Popa TA, Ladea M. Nutrition and depression at the forefront of progress. J Med Life. 2012;5(4):414-419.
Sarris J, O’Neil A, Coulson CE, Schweitzer I, Berk M. Lifestyle medicine for depression. BMC Psychiatry. 2014;14(1):107. https://doi.org/10.1186/1471-244X-14-107
Tiong CP, Loke AC, Mohamed Z, Zainal NZ. Serotonin transporter gene polymorphism is associated with antidepressant response to escitalopram in multiethnic Malaysians with major depressive disorder: a preliminary study. Malay J Psychiatr. 2013;22(2):59-71.
Vandenbergh DJ, Persico AM, Hawkins AL, Griffin CA, Li X, Jabs EW, et al. Human dopamine transporter gene (DAT1) maps to chromosome 5p15.3 and displays a VNTR. Genomics. 1992;14(4):1104-1106. https://doi.org/10.1016/S0888-7543(05)80138-7
Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388(10053):1545-1602. https://doi.org/10.1016/S0140-6736(16)31678-6
Willner P. The mesolimbic dopamine system as a target for rapid antidepressant action. Int Clin Psychopharmacol. 1997; 12(Suppl 3):S7-S14. http://dx.doi.org/10.1097/00004850-199707003-00002
Zhou K, Chen W, Buitelaar J, Banaschewski T, Oades RD, Franke B, et al. Genetic heterogeneity in ADHD: DAT1 gene only affects probands without CD. Am J Med Genet. 2008;147B(8):1481-1487. https://doi.org/10.1002/ajmg.b.30644
Copyright (c) 2019 Asraa Aldoghachi, Pike-See Cheah, Normala Ibrahim, Munn Sann Lye, King-Hwa Ling
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The observations and associated materials published or posted by NeurosciRN are licensed by the authors for use and distribution in accord with the Creative Commons Attribution license CC BY-NC 4.0 international, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.