Gene polymorphism of the dopamine transporter and dopamine receptor D2 is associated with physique

DOI: 10.33876/2311-0546/2020-52-4/232-248

Abstract

One of the topical interdisciplinary areas of scientific research is the study of the mechanisms underlying the formation of the human constitution. The polymorphism of the neurotransmitter systems genes is quite often considered in connection with various aspects of the human psyche and physique. The aim of the present study is to search for the associations of the dopamine transporter and dopamine D2 receptor gene polymorphisms with physique and functional characteristics of the cardiovascular system. The anthropogenetic examination of 216 males and females aged 16-23 years was conducted in the Republic of Mordovia. The body length and weight, the waist and hips circumferences, the skinfolds thickness on the trunk and extremities were measured, while the systolic and diastolic blood pressure, heart rate were determined as the functional indicators of the cardiovascular system. All respondents were genotyped at the loci 3ˊ-UTR VNTR DAT1 of the dopamine transporter and DRD2/ANKK1 Taq1A (rs1800497) of the second type dopamine receptor. Significant (p<0.05) associations were found using the Mann-Whitney U-test (a comparative analysis of the average values) of morphofunctional indicators in people with different genotypes of the studied genes. Females with at least one allele 9 at the DAT1 are characterized by higher body weight and waist circumference compared with those with genotype 9-. Female carriers of the C/C genotype at the DRD2/ANKK1 Taq1A demonstrated higher indicators of body mass, body mass index, waist circumference, abdominal, triceps and thigh skinfolds, as well as a higher heart rate compared to other female genotypes. There were no significant differences in morphofunctional characteristics for males. The revealed associations of the polymorphism of the DAT1 and DRD2 with morphofunctional characteristics are probably due to the complex influence of genetic factors on the formation of body features. The results can be used in personalized medicine.

References

1. Ariza, M., M. Garolera, M.A. Jurado, I. Garcia-Garcia, I. Hernan, C. Sánchez-Garre, M. Vernet-Vernet, M.J. Sender-Palacios, I. Marques-Iturria, R. Pueyo, B. Segura, and A. Narberhaus. Dopamine Genes (DRD2/ANKK1-TaqA1 and DRD4–7R) and Executive Function: Their Interaction with Obesity. PLoS One 7 (7): e41482. https://doi.org/10.1371/journal.pone.0041482
2. Avsar, O., A. Kuskucu, S. Sancak, and E. Genc. 2017. Are dopaminergic genotypes risk factors for eating behavior and obesity in adults? Let. 654: 28–32. https://doi.org/10.1016/j.neulet.2017.06.023
3. Benton, D., and H.A. Young. 2016. A meta-analysis of the relationship between brain dopamine receptors and obesity: a matter of changes in behavior rather than food addiction? J. Obes. 40 (1): S12–S21. https://doi.org/10.1038/ijo.2016.9
4. Bieliński, M., M. Jaracz, N. Lesiewska, M. Tomaszewska, M. Sikora, R. Junik, A. Kamińska, A. Tretyn, and A. 2017. Association between COMT Val158Met and DAT1 polymorphisms and depressive symptoms in the obese population. Neuropsychiatr. Dis. Treat. 13: 2221–2229. https://doi.org/10.2147/NDT.S138565
5. Bondareva, E.A., M.A. Negasheva, A.V. Grudieva, and T.V. Tarasova. 2016. Assotsiatsii T/A-polimorfizma gena FTO s kharakterom zhirootlozheniia u iunoshei i devushek [T/A-polymorphism of the FTO gene is associated with fat accumulation traits in youngsters]. Vestnik Moskovskogo Universiteta. Seria XXIII. Antropologia 4: 69–77.
6. Butovskaya, P.R., M.L. Butovskaya, V.A. Vasilyev, O.E. Lazebny, D.V. Shibalev, E.V. Veselovskaya, I.G. Udina, and A.P. Ryskov. 2013. Molecular-genetic polymorphisms of dopamine, serotonin and androgenic systems as molecular markers of success in judo wrestling sportsmen. Bioanal. Biomed. S3: 005. https://doi.org/10.4172/1948-593X.S3-005
7. Costa, A., M. Riedel, U. Müller, H.J. Möller, and U. Ettinger. 2011. Relationship between SLC6A3 genotype and striatal dopamine transporter availability: A meta‐analysis of human single photon emission computed tomography studies. Synapse 65 (10): 998–1005. https://doi.org/10.1002/syn.20927
8. Davis, C., K. Patte, R. Levitan, C. Reid, S. Tweed, and C. Curtis. 2007. From motivation to behaviour: a model of reward sensitivity, overeating, and food preferences in the risk profile for obesity. Appetite 48 (1): 12–19. https://doi.org/10.1016/j.appet.2006.05.016
9. Davis, C., R.D. Levitan, Z. Yilmaz, A.S. Kaplan, J.C. Carter, and J.L. Kennedy. 2012. Binge eating disorder and the dopamine D2 receptor: genotypes and sub-phenotypes. Neuropsychopharmacol. Biol. Psychiatry 38 (2): 328–335. https://doi.org/10.1016/j.pnpbp.2012.05.002
10. Doehring, A., N. Hentig, J. Graff, S. Salamat, M. Schmidt, Geisslinger, S. Harder, and J. Lotsch. 2009. Genetic variants altering dopamine D2 receptor expression or function modulate the risk of opiate addiction and the dosage requirements of methadone substitution. Pharmacogenet. Genomics 19 (6): 407–414. https://doi.org/10.1097/FPC.0b013e328320a3fd
11. Eubanks, J.H., M. Djabali, L. Selleri, D.K. Grandy, O. Civelli, D.L. McElligott, and G.A.Evans. 1992. Structure and linkage of the D2 dopamine receptor and neural cell adhesion molecule genes on human chromosome 11q23. Genomics 14 (4): 1010–1018. https://doi.org/10.1016/s0888-7543(05)80124-7
12. Flegontova, O.V., A.V. Khrunin, O.I. Lylova, L.A. Tarskaia, V.A. Spitsyn, A.I. Mikulich, and S.A. Limborska. 2009. Haplotype frequencies at the DRD2 locus in populations of the East European Plain. BMC Genet. 10: 62. https://doi.org/10.1186/1471-2156-10-62
13. Giros, B., and M.G. Caron. 1993. Molecular characterization of the dopamine transporter. Trends Pharmacol. Sci. 14 (2): 43–49. https://doi.org/10.1016/0165-6147(93)90029-j
14. Hu, Y., J. Hakkola, M. Oscarson, M. Ingelman-Sundberg. 1999. Structural and Functional Characterization of the 5'-flanking Region of the Rat and Human Cytochrome P450 2E1 Genes: Identification of a Polymorphic Repeat in the Human Gene. Biophys. Res. Commun. 263 (2): 286–293. https://doi.org/10.1006/bbrc.1999.1362
15. Kalmin, O.V., Yu.S. Afanasievskaia, and A.V. Samotuga. 2010. Otsenka osobennostei antropometricheskikh parametrov raspredeleniia somatotipov lits iunosheskogo vozrasta goroda Krasnodara i Krasnodarskogo Kraia [Assessment of the characteristics of the anthropometric parameters of the distribution of somatotypes of young people of Krasnodar and the Krasnodar Territory]. Izvestiia vysshikh uchebnykh zavedenii. Povolzhskii region. Meditsinskie nauki 1 (13): 3–11.
16. Kolokoltsev, M.M., and V.Yu. Lebedinsky. 2012. Sravnitel'naia kharakteristika urovnia fizicheskogo razvitiia studencheskoi molodezhi iunosheskogo vozrasta Irkutskoi oblasti [Comparative characteristics of level of physical development of young students of Irkutsk]. Biulleten' VSNC SO RAMN 6 (88): 47–54.
17. Krause, J., S.H. Dresel, K.H. Krause, C. La Fougère, P. Zill, and M. Ackenheil. 2006. Striatal dopamine transporter availability and DAT–1 gene in adults with ADHD: no higher DAT availability in patients with homozygosity for the 10-repeat allele. World J. Biol. Psychiatry 7 (3): 152–157. https://doi.org/10.1080/15622970500518444
18. Negasheva, M.A. 2017. Osnovy antropometrii [Basics of Anthropometry]. Moscow: Ekon-Inform.
19. Nymberg, C., T. Banaschewski, A.L. Bokde, C. Büchel, P. Conrod, H. Flor, V. Frouin, H. Garavan, P. Gowland, A. Heinz, B. Ittermann, K. Mann, J.L. Martinot, F. Nees, T. Paus, Z. Pausova, M. Rietschel, T.W. Robbins, M.N. Smolka, A. Ströhle, G. Schumann, and T. Klingberg. 2014. DRD2/ANKK1 polymorphism modulates the effect of ventral striatal activation on working memory performance. Neuropsychopharmacology 39 (10): 2357–2365. https://doi.org/10.1038/npp.2014.83
20. Palmeira, L., M.Cunha, C. Padez, M. Alvarez, J. Pinto-Gouveia, and Manco. 2019. Association study of variants in genes FTO, SLC6A4, DRD2, BDNF and GHRL with binge eating disorder (BED) in Portuguese women. Psychiatry Res. 273: 309–311. https://doi.org/10.1016/j.psychres.2019.01.047
21. Rand, C.M., P.P. Patwari, E.A. Rodikova, L. Zhou, E.M. Berry-Kravis, R.J. Wilson, T. Bech-Hansen, and D.E. Weese-Mayer. 2011. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation: analysis of hypothalamic and autonomic candidate genes. Res. 70 (4): 375–378. https://doi.org/10.1203/PDR.0b013e318229474d
22. Rivera-Iñiguez, I., A. Panduro, O. Ramos-Lopez, S.J. Villaseñor-Bayardo, and S. Roman. 2019. DRD2/ANKK1 TaqI A1 polymorphism associates with overconsumption of unhealthy foods and biochemical abnormalities in a Mexican population. Weight. Disord. 24 (5): 835–844. https://doi.org/10.1007/s40519-018-0596-9
23. Savitz, J., C.A. Hodgkinson, C. Martin-Soelch, P.H. Shen, J. Szczepanik, A.C. Nugent, P. Herscovitch, A.A. Grace, D. Goldman, and W.C. Drevets. 2013. DRD2/ANKK1 Taq1A polymorphism (rs1800497) has opposing effects on D2/3 receptor binding in healthy controls and patients with major depressive disorder. J. Neuropsychopharmacol. 16 (9): 2095–2101. https://doi.org/10.1017/S146114571300045X
24. Sikora, M., A. Gese, R. Czypicki, M. Gąsior, A. Tretyn, J. Chojnowski, M. Bieliński, M. Jaracz, A. Kamińska, R. Junik, and A. Borkowska. 2013. Correlations between polymorphisms in genes coding elements of dopaminergic pathways and body mass index in overweight and obese women. Pol. 64 (2): 101–107.
25. Sineva, I.M., M.A. Negasheva, and Yu.M. Popov. 2017. Sravnitel'nyi analiz urovnia fizicheskogo razvitiia studentov raznykh gorodov Rossii [Comparative analysis of physical development of students from different cities of Russia]. Vestnik Moskovskogo Universiteta. Seria XXIII. Antropologia 4: 17–27.
26. Smith, C.T., L.C. Dang, J.W. Buckholtz, A.M. Tetreault, R.L. Cowan, R.M. Kessler, and D.H. Zald. 2017. The impact of common dopamine D2 receptor gene polymorphisms on D2/3 receptor availability: C957T as a key determinant in putamen and ventral striatum. Psychiatry 7 (4): e1091. https://doi.org/0.1038/tp.2017.45
27. Stice, E., K.S. Burger, and S. Yokum. 2015. Reward Region Responsivity Predicts Future Weight Gain and Moderating Effects of the TaqIA Allele. Neurosci. 35 (28): 10316–10324. https://doi.org/10.1523/JNEUROSCI.3607-14.2015
28. Stice, E., S. Spoor, C. Bohon, and D.M. Small. 2008. Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele. Science 322 (5900): 449–452. https://doi.org/10.1126/science.1161550
29. Uzun, M., E. Saglar, S. Kucukyildirim, B. Erdem, H. Unlu, and H. Mergen. 2015. Association of VNTR polymorphisms in DRD4, 5-HTT and DAT1 genes with obesity. Physiol. Biochem. 121 (2): 75–79. https://doi.org/10.3109/13813455.2014.985686
30. Van Dyck, C.H., R.T. Malison, L.K. Jacobsen, J.P. Seibyl, J.K. Staley, M. Laruelle, R.M. Baldwin, R.B. Innis, and J. Gelernter. 2005. Increased dopamine transporter availability associated with the 9-repeat allele of the SLC6A3 gene. Nucl. Med. 46 (5): 745–751.
31. Vandenbergh, D.J., A.M. Persico, A.L. Hawkins, C.A. Griffin, X. Li, E.W. Jabs, and G.R. Uhl. 1992. Human dopamine transporter gene (DAT1) maps to chromosome 5p15. 3 and displays a VNTR. Genomics 14 (4): 1104–1106. https://doi.org/10.1016/s0888-7543(05)80138-7
32. VanNess, S.H., M.J. Owens, and C.D. Kilts. 2005. The variable number of tandem repeats element in DAT1 regulates in vitro dopamine transporter density. BMC Genet. 6 (1): 55. https://doi.org/10.1186/1471-2156-6-55
33. Viazova, L.S., and A.V. Solntseva. 2018. Vzaimnoe vliianie geneticheskogo polimorfizma TaqIA gena dofaminovogo retseptora 2 tipa, urovnei dofamina i leptina krovi na formirovanii raznykh form ozhireniia u detei [Mutual effect of TaqIA genetic polymorphism of the dopamine receptor type 2 gene, levels of dopamine and blood leptin on the formation of various forms of obesity in children]. Detskaia meditsina Severo-Zapada 7 (1):71.
34. Winkler, J.K., A. Woehning, J.-H. Schultz, M. Brune, N. Beaton, D. Challa, S. Minkova, E. Roeder, P.P. Nawroth, H.C. Friederich, C. Wolfrum, and G. Rudofsky. 2012. TaqIA polymorphism in dopamine D2 receptor gene complicates weight maintenance in younger obese patients. Nutrition 28 (10): 996–1001. https://doi.org/10.1016/j.nut.2011.12.018