Abstract
Introduction: in the 3’ Untranslated Region (UTR) of the SLC6A3 gene coding for the dopamine transporter 1 (DAT1), the presence of Variable Number Tandem Repeats (VNTR) has been described that, depending on their length, can affect protein expression and dopaminergic reuptake, which could contribute to the development of neuropsychiatric disorders such as anxiety and depression. Objective: to describe the frequency of VNTR polymorphisms in the 3’ UTR region of the DAT1 gene in a sample of undergraduate students with low levels of depression and anxiety from a private university in Cali, Colombia. Methods: cross-sectional study in 62 college students aged 18-25 years in 2018, selected with low levels of anxiety and depression according to Beck Depression Inventory (BDI -II) and Beck Anxiety Inventory (BAI) inventories. VNTR polymorphisms of the SLC6A3 gene for DAT-1 were genotyped from peripheral blood DNA from PCR technique. Hardy Weinberg equilibrium was calculated with the frequencies. Results: fifty-two percent of the subjects were female, with a mean age of 20 years. The genotypic frequencies of DAT1 VNTRs were in Hardy- Weinberg equilibrium (p > 0.05). The alleles with the highest frequency were VNTRs with 10R (75 %) and 9R (23.4 %). Rare alleles of 11R and 6R (0.08 %) were found to be present in heterozygous genotypes with 10R. Conclusion: the 10R and 9R allele frequencies of VNTR DAT-1 in university students with low levels of depression and anxiety were similar to those reported in other Latin American populations. The less frequent 6R and 11R variants may derive from interbreeding with Asian or European populations.
References
McHugh PC, Buckley DA. The structure and function of the dopamine transporter and its role in CNS diseases. Vitam Horm. 2015;98:339–369.
Bahena-Trujillo R, Flores G, Arias-Montaño JA. Dopamina: síntesis, liberación y receptores en el Sistema Nervioso Central. Rev Biomed. 2000;11(1):39–60.
Kawarai T, Kawakami H, Yamamura Y, Nakamura S. Structure and organization of the gene encoding human dopamine transporter. Gene. 1997;195(1):11-18.
Mitchell RJ, Howlett S, Earl L, White NG, McComb J, Schanfield MS, et al. Distribution of the 3’ VNTR polymorphism in the human dopamine transporter gene in world populations. Hum Biol. 2000;72(2):295–304.
Kang AM, Palmatier MA, Kidd KK. Global variation of a 40-bp VNTR in the 3’-untranslated region of the dopamine transporter gene (SLC6A3). Biol Psychiatry. 1999;46(2):151–160.
VanNess SH, Owens MJ, Kilts CD. The variable number of tandem repeats element in DAT1 regulates in vitro dopamine transporter density. BMC Genet. 2005;6:55.
Kurian MA, Zhen J, Cheng SY, Li Y, Mordekar SR, Jardine P, et al. Homozygous loss-offunction mutations in the gene encoding the dopamine transporter are associated with infantile parkinsonism-dystonia. J Clin Invest. 2009;119(6):1595-603.
Gafarov VV, Gromova EA, Maksimov VN, Gagulin I V, Gafarova AV. Association of personal anxiety with dopamine receptor D4 (DRD4), DAT genes polymorphism. En: Kalinin V, Hocaoglu C y Shafizan M. Anxiety Disorders - The New Achievements. IntechOpen; 2021.
Kirchheiner J, Nickchen K, Sasse J, Bauer M, Roots I, Brockmöller J. A 40-basepair VNTR polymorphism in the dopamine transporter (DAT1) gene and the rapid response to antidepressant treatment. Pharmacogenomics J. 2007;(1):48–55.
Gadow KD, Roohi J, DeVincent CJ, Hatchwell E. Association of ADHD, tics, and anxiety with dopamine transporter (DAT1) genotype in autism spectrum disorder. J Child Psychol Psychiatry. 2008;49(12):1331-1338.
Estados Unidos de América. Washington, D.C. Organización Panamericana de la Salud. Depresión y otros trastornos mentales comunes. Estimaciones sanitarias mundiales. Institutional Repository for Information Sharing; 2017.
Gómez C, de Santacruz C, Rodriguez MN, Rodriguez V, Tamayo N, Matallana D, et al. Encuesta Nacional de Salud Mental Colombia 2015. Protocolo del estudio. Rev Colomb de Psiquiat. 2016;45(1):2–8.
Sanabria JP, Useche B, Ochoa PP, Rojas DF, Mateo C, Carmona M, et al. Social Inequities in the Impact of COVID-19 Lockdown Measures on the Mental Health of a Large Sample of the Colombian Population (PSY-COVID Study). J Clin Med. 2021 ;10(22):5297.
Saung WT, Narasimhan S, Lohoff FW. Lack of influence of DAT1 and DRD2 gene variants on antidepressant response in generalized anxiety disorder. Hum Psychopharmacol. 2014;29(4):316-21.
Londoño NH, Calle LC, Rojas ZB. Depresión y ansiedad en estudiantes que ingresan a la universidad y factores de estrés asociados. Rev. Psicol. Saúde. 2021;13(4):121–138.
Saenz J, Perdigón A, Vázquez C. Adaptación española del inventario para la depresión de Beck-II (BDI-II): 2. Propiedades psicométricas en población general. Clin Salud. 2003;14(3):249- 280.
Maldonado N, Castro R, Cardona P. Propiedades psicométricas del Inventario de Depresión de Beck-II (BDI-II) en población universitaria colombiana. Rev Colomb Psiquiatr. 2021. Available from: http://dx.doi.org/10.1016/j. rcp.2021.08.007
Sanz J, Fréderique V, Guía E, Hernández A. Inventario de Ansiedad de Beck (BAI) [Internet]. Madrid: Consejo general de Colegios Oficiales de Psicólogos;2011. Available from: https://www.Losada-CasallasKD.cop.es/uploads/PDF/2013/BAI.pdf
Cabrera E, Charry SA, Astaiza G. Asociación entre depresión, ansiedad, estrés y lugar de origen (migración interna-no migración) en estudiantes universitarios. Psicología y Salud. 2023;33(2):477- 86.
Erazo MI, Jiménez MDC. Dimensiones psicopatológicas en estudiantes universitarios. CES PSICO. 2012;5(1):65-76.
Klimenko O, Hernández N, Álvarez JL, Paniagua KY. La ansiedad y su relación con las estrategias de afrontamiento en una muestra de universitarios en el marco de la pandemia de COVID-19. Psicoespacios. 2023;17(30):1-18.
Salazar IC, Varela MT, Lema LF, Tamayo JA, Duarte C. Evaluación de las conductas de salud en jóvenes universitarios. Rev Salud Pública. 2010;12(4):599-611.
Waldman ID, Rowe DC, Abramowitz A, Kozel ST, Mohr JH, Sherman SL, et al. 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. 1998;63(6):1767–76.
Graffelman J, Weir BS. Multi-allelic exact tests for Hardy-Weinberg equilibrium that account for gender. Mol Ecol Resour. 2018;18(3):461–73.
Iniesta R, Guinó E, Moreno V. Análisis estadístico de polimorfismos genéticos en estudios epidemiológicos. Tac Sanit. 2005;19(4):333-341.
Team, R. C. R: a language and environment for statistical computing. R proyect. [Internet]. 2019. Available from: https://www.gbif.org/ tool/81287/r-a-language-and-environment-forstatistical-computing
Vieyra SG, Moraga MV, Henríquez BH, Aboitiz DF, Rothhammer EF. Distribución de alelos de los genes DRD4 y DAT1 del sistema dopaminérgico en la población mixta de Santiago de Chile. Rev Med Chil. 2003;131(2):135–143.
Silva MA, Cordeiro Q, Miracca EC, Guindalini C, Vallada H. Distribucion de alelos del polimorfismo VNTR en la región 3’no codificante del gen del DAT1 (SLC6A3) en São Paulo/Brasil y su importancia para los estudios genéticos de los trastornos neuropsiquiátricos en poblaciones mixtas. Rev Med Chil. 2005;133(11):1392-1393.
Ortega J, Arboleda CE, Morales L, Benítez BA, Beltrán D, Izquierdo Á, et al. Estudio de variantes de los genes BDNF, COMT, DAT1 y SERT en niños colombianos con déficit de atención. Rev Colomb Psiquiatr. 2017;46(4):222–228.
Persico AM, Macciardi F. Genotypic association between dopamine transporter gene polymorphisms and schizophrenia. Am J Med Genet. 1997;74(1):53–57.
Holmes J, Payton A, Barrett JH, Hever T, Fitzpatrick H, Trumper AL, et al. A family-based and casecontrol association study of the dopamine D4 receptor gene and dopamine transporter gene in attention deficit hyperactivity disorder. Mol Psychiatry. 2000;5(5):523–530.
Mayo O. A Century of Hardy–Weinberg Equilibrium. Twin Res Hum Genet. 2008;11(3):249– 256.
Greenwood TA, Kelsoe JR. Promoter and intronic variants affect the transcriptional regulation of the human dopamine transporter gene. Genomics. 2003;82(5):511–520.
Dunn EC, Brown RC, Dai Y, Rosand J, Nugent NR, Amstadter AB, et al. Genetic determinants of depression: recent findings and future directions. Harv Rev Psychiatry. 2015;231:1–18.
Gururajan A, Cryan JF, Dinan TG. Chapter 26 - Molecular biomarkers in depression: Toward personalized psychiatric treatment. In: Baune BT, editor. Personalized Psychiatry. San Diego: Academic Press; 2020. p. 319–338.
Murphy DL, Lerner A, Rudnick G, Lesch KP. Serotonin transporter: gene, genetic disorders, and pharmacogenetics. Mol Interv. 2004;42:109– 123.
López-León S, Janssens ACJW, GonzálezZuloeta Ladd AM, Del-Favero J, Claes SJ, Oostra BA, et al. Meta-analyses of genetic studies on major depressive disorder. Mol Psychiatry. 2008;13(8):772–785.
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