The -141c Ins/Del polymorphism of the D₂-dopaminergic receptor gene as a marker of early development of essential arterial hypertension in adolescents

Background. The relevance of the search for genetic markers of essential hypertension (EH), is beyond doubt. The importance of research of dopaminergic system genes consists primarily of pleiotropic effects of dopamine on different systems and functions of the body. The aim of this study was to identify the association of polymorphism -141C 1/D D2-dopaminergic receptor (DRD2) with parameters of psycho-vegetative status and cardiovascular system indicators in adolescents with EH. Methods. We carried out an investigation of 14-17-year old (15.92 ± 1.12) Caucasian male patients with EH (n = 110) in clinic of Scientific Centre for Family Health and Human Reproduction Problems. Psychological testing, clinoorthostatic test, ambulatory blood pressure monitoring (ABPM), and genotyping have been carried. Results. 11-genotype is associated with higher «hypomania» personality traits (scale 9 of Mini-SMIL was 4.2 (4-5) in carriers of the 11-genotype and 4.0 (3-4) in 1D and DD-genotype carriers, p = 0.024), asthenosympathicotonic variant of autonomic support and pressure load (ejection fraction in carriers of the 11-genotype was 71.47 ± 5.98 % and 68.44 ± 6.01 % in 1D and DD-genotype carriers, p = 0.044, time of systolic blood pressure hypertension in carriers of the 11-genotype - 35.50 (20.5-51.5) and 18.30 (6.5-32) - in 1D and DD-genotype carriers, p = 0.010, the time of diastolic blood pressure hypertension in 11-genotype carriers was 13 (7.85-26.5) and 2 (0.9-11) - in 1D and DD-genotype carriers, p = 0,002). Conclusion. -141C I/D DRD2 polymorphism is associated with disorders of important indicators of psycho-vegetative status and cardiovascular system, including circadian organization of blood pressure, which allows considering it as a marker of early development of EH in adolescents.

-141С I/D DRD, adolescents, essential hypertension, -141С I/D DRD, psychology, vegetative status

1. Белоконь Н.А., Кубергер М.Б. Болезни сердца и сосудов у детей: руководство для врачей: в 2-х т. - М.: Медицина, 1987. - Т. 1. - 245 с

2. Кибитов А.О., Курылев А.А., Бродянский В.М., Чупрова Н.А., Иващенко Д.В., Сулимов Г.Ю., Андреев Б.В. Сочетание полиморфизмов генов дофаминового рецептора типа 2 (DRD2 -141C INS/DEL) и протеинкиназы PKK2 (DRD2/ANKK1 TAQ1A) снижает генетический риск развития параноидной шизофрении // Социальная и клиническая психиатрия. -2017. - T. 27, № 3. - C. 63-72

3. Колесникова Л.И., Долгих В.В., Поляков В.М., Рычкова Л.В., Мадаева И.М., Погодина А.В., Протопопова О.Н. Психофизиологические взаимоотношения при артериальной гипертензии в онтогенезе // Сибирский научный медицинский журнал. - 2009. - T. 139, № 5. - С. 79-85

4. Колесникова Л.И., Калюжная О.В., Рычкова Л.В., Косовцева А.С., Ершова О.А., Мандзяк Т.В., Баирова Т.А. Ген аполипопротеина-Виего роль в формировании эссенциальной артериальной гипертензии // Бюл. ВСНЦ СО РАМН. - 2015. - Т. 106, № 6. - С. 58-61

5. Косовцева А.С., Колесникова Л.И., Рычкова Л.В., Поляков В.М., Баирова Т.А. Ген а2а-адренорецептора и личностные особенности у подростков с эссенциальной артериальной гипертензией // Педиатрия им Г.Н. Сперанского. - 2017. - Т. 96, № 3. - С. 34-39

6. Криволапчук И.А., Зайцева Г.А., Криволапчук И.И., Буслаков А.П., Носова Р.М., Бондарева С.А. Стрессовая реактивность сердечно-сосудистой системы у школьников в период второго детства // Новые исследования. - 2014. - Т. 40, № 3. - С. 20-30

7. Личко А.Е. Психопатии и акцентуации характера у подростков. - СПб.: Речь, 2010. - 256 с

8. Собчик Л.Н. Психолог о подростках в школе и семье // Московский психологический журнал. -2002. - № 3

9. Akiskal H/S. (1983). Diagnosis and treatment of affective disorders. Psychiat Clin N Amer, (6), 210-215.

10. Al-Eitan L.N., Jaradat S.A., Hulse G.K., Tay G.K. (2012). Custom genotyping for substance addiction susceptibility genes in Jordanians of Arab descent. BMC Res Notes, (5), 497-505.

11. Arinami T., Gao M., Hamaguchi H., Toru M. (1997). A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia. Hum Mol Genet, (6), 577-582.

12. Bergson C., Levenson R., Goldman-Rakic P.S., Lidow M.S. (2003). Dopamine receptor-interacting proteins: the Ca(2+) connection in dopamine signaling. Trends Pharmacol Sci, (24), 486-492.

13. De Mei C., Ramos M., Iitaka C., Borrelli E. (2009). Getting specialized: presynaptic and postsynaptic dopamine D2 receptors. Curr Opin Pharmacol, (9), 53-58.

14. DeJean D., Giacomini M., Vanstone M., Brundisini F. (2013). Patient experiences of depression and anxiety with chronic disease. A systematic review and qualitative meta-synthesis. Ont Health Technol Assess Ser, 13 (16), 1-33.

15. GeneCards. Human gene database. Available at: http://www.genecards.org/cgi-bin/carddisp.pl?gene=DRD2.

16. Himei A., Koh J., Sakai J., Inada Y., Akabame K., Yoneda H. (2002). The influence on the schizophrenic symptoms by the DRD2Ser/Cys311and -141C Ins/ Del polymorphisms. Psychiatry Clin Neurosci, 56 (1), 97-102.

17. Jonsson E.G., Nothen M.M., Grunhage F., Farde L., Nakashima Y., Propping P., Sedvall G.C. (1999). Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers. Mol Psychiatry, (4), 290-296.

18. Kurt H., Dikmen M., Basaran A., Yenilmez C., Ozdemir F., Degirmenci I., Gunes H.V., Kucuk M.U., Mutlu F. (2011). Dopamine D2 receptor gene -141C insertion/ deletion polymorphism in Turkish schizophrenic patients. Mol Biol Rep, 38 (2), 1407-1411.

19. Paik S.H., Choi M.R., Kwak S.M., Bang S.H., Chun J.W., Kim J.Y., Choi J., Cho Hyun, Jeong J.E., Kim D.J. (2017). An association study of Taq1A ANKK1 and C957T and - 141C DRD2 polymorphisms in adults with internet gaming disorder: a pilot study. Ann Gen Psychiatry, (16), 45.

20. Parsian A., Cloninger C.R., Zhang Z.H. (2000). Functional variant in the DRD2 receptor promoter region and subtypes of alcoholism. Am J Med Genet, (96), 407-411.

21. Prasad P., Kumar K.M.P., Ammini A.C., Gupta A., Gupta R., Thelma B.K. (2008). Association of dopaminergic pathway gene polymorphisms with chronic renal insufficiency among Asian Indians with type-2 diabetes. BMC Genetics, (9), 26.

22. Ritchie T., Noble E.P. (2003). Association of seven polymorphisms of the D2 dopamine receptor gene with brain receptor binding characteristics. Neurochem Res, 28 (1), 73-82

23. Stein D.J., Aguilar-Gaxiola S., Alonso J., Bruffaerts R., de Jonge P., Liu Z., Caldas-de-Almeida J.M., O’Neill S., Viana M.C., de Graaf R., Ferry F., Kovess-Masfety V., Levinson D., de Girolamo G., Florescu S., Hu C., Kawakami N., Haro J.M., Piazza M., Posada-Villa J., Wojtyniak B.J., Xavier M., Lim C.C.W., Kessler R.C., Scott K.M. (2014). Associations between mental disorders and subsequent onset of hypertension. Gen Hosp Psychiatry, (36), 142-149.

24. Xiao L., Shen T., Peng D.H., Shu C., Jiang K.D., Wang G.H. (2013). Functional -141C Ins/Del polymorphism in the dopamine D2 receptor gene promoter and schizophrenia in a Chinese Han population. J 1nt Med Res, 41 (4), 1171-1178.

25. Zahari Z., Teh L.K., Ismail R., Razali S.M. (2011). Influence of DRD2 polymorphisms on the clinical outcomes of patients with schizophrenia. Psychiatr Genet, 2 (4), 183-189.

26. Zhang Y., Cuevas S., Asico L.D., Escano C., Yang Y., Pascua A.M., Wang X., Jones J.E., Grandy D., Eisner G., Jose P.A., Armando I. (2012). Deficient dopamine D2 receptor function causes renal inflammation independently of high blood pressure. PLoS One, 6 (7), 1-11.