Analysis of associations of the RS1 microsatellite locus of the arginine-vasopressin receptor gene (AVPR1A) with the level of hormones of the anterior lobe of the pituitary gland and variations in personality traits in the yakut population

To study the role of genetic factors in personality traits development and possible association with the hormonal status of an individual, it is relevant to analyze the polymorphism of genes affecting mental processes, in particular, the arginine-vasopressin receptor gene (AVPR1A). The aim of this study was to search for associations of the microsatellite locus RS1, which affects f AVPR1A expression level, with the hormones level of the anterior lobe of the pituitary gland and personality traits in the Yakut population. The study sample included Yakut men aged 18-26 years (n=121). Analysis of the number of RS1 repeats was carried out using PCR method and sequencing of the primary nucleotide sequence. Serum hormone levels were determined by enzyme-linked immunosorbent assay (ELISA). In the Yakut population alleles and genotypes frequencies of the AVPR1A RS1 locus have been determined, “short” (S) alleles containing ≤10 repeats (63%) and the corresponding SS genotypes (44.6%) were more frequent, while individuals with “long” (LL) and “heterozygous” (SL) genotypes accounted for 18.2% and 37.2%, respectively. To search for a possible association between the AVPR1A RS1 locus and the hormonal status of Yakut men, we analyzed associations between the SS, SL, and LL genotypes and the level of hormones of the anterior lobe of the pituitary gland such as ACTH, TSH, FSH, and LH. The range of concentrations of ACTH and TSH in the group of individuals with SS genotypes was significantly lower than that observed in the group of LL genotype-carriers (p=0.042 and p=0.048, respectively), and the LH level, on the contrary, was statistically significantly higher (p=0.029). When searching for associations between genotypes of the RS1 AVPR1A locus and individual variance in personality traits, it was found that individuals with SS genotypes demonstrated statistically significant increase in such personality traits as “novelty seeking” (p=0.02) and “reward dependence ” (p=0.01) compared to LL genotypes. The results obtained indicate the modulating effect of genetic variants of the AVPR1A gene in the formation of interindividual differences in the level of hormones of the anterior lobe of the pituitary gland, which could affect the manifestation of psychoemotional sphere in humans.

Arginine Vasopressin, AVPR1A gene, Yakuts, personality traits, hormones ACTH, TSH, FSH, LH

1. Benjamin J,. Ebstein R.P., Belmaker R.H. Personality genetics. Isr. J. Psychiatry Relat. Sci. 2002; 39(4):271-279.

2. Caspi A., Roberts B.W., Shiner R.L. Personality development: stability and change. Annu. Rev. Psychol. 2005;56:453-484.doi: 10.1146/annurev.psych.55.090902.141913

3. Srivastava S., John O.P. Gosling S.D., Potter J. Development of personality in early and middle adulthood: set like plaster or persistent change? J. Pers. Soc. Psychol. 2003;84(5):1041-1053. doi: 10.1037/0022-3514.84.5.1041

4. Белокоскова С.Г., Цигунов С.Г. Вазопрессин в механизмах реализаций реакций на стресс и модуляции эмоций. Обзоры по клинической фармакологии и лекарственной терапии. 2018;16(3):5-12. doi: 10.17816/RCF1635-12

5. Yirmiya N., Rosenberg C., Levi S. et al. Association between the arginine vasopressin 1a receptor (AVPR1a) gene and autism in a family-based study: mediation by socialization skills. Mol. Psychiatry. 2006;11(5):488-494. doi: 10.1038/sj.mp.4001812

6. Meyer-Lindenberg A., Kolachana B., Gold B. et al. Genetic variants in AVPR1A linked to autism predict amygdala activation and personality traits in healthy humans. Mol. Psychiatry. 2009; 14:968-975. doi: 10.1038/mp.2008.54

7. Tansey K.E., Hill M.J., Cochrane L.E. et al. Functionality of promoter microsatellites of arginine vasopressin receptor 1A (AVPR1A): implications for autism. Mol.Autism. 2011; 2(1):3. doi: 10.1186/2040-2392-2-3

8. Казанцева А.В., Кутлумбетова Ю.Ю., Малых С.Б. и др. Ассоциация полиморфных маркеров генов аргинин-вазопрессиновых рецепторов (AVPR1A и AVPR1B) с чертами личности. Генетика. 2014;50(3):341-352.

9. Yang S.Y., Kim S.A., Hur G.M. et al. Replicative genetic association study between functional polymorphisms in AVPR1A and social behavior scales of autism spectrum disorder in the Korean population. Molecular Autism. 2017; 8:44. doi: 10.1186/s13229-017-0161-9

10. Kazantseva A., Davydova Y, Enikeeva R. et al. AVPR1A main effect and OXTR-by-enviroment interplay in individual differences in depression level. Heliyon. 2020;6(10): e05240. doi: 10.1016/j.heliyon.2020.e05240.

11. Zhang Y., Zhu D., Zhang P. et al. Neural mechanisms of AVPR1A RS3-RS1 haplotypes that impact verbal learning and memory. Neuroimage. 2020;222:117283. doi: 10.1016/j.neuroimage.2020.117283

12. Bachner-Melman R., Dina C., Zohar A.H. et al. AVPR1A and SLC6A4 gene polymorphisms are associated with creative dance performance. PLoS Genet. 2005;1(3):394-403. doi: 10.1371/journal.pgen.0010042

13. Ukkola L.T., Onkamo P., Raijas P. et al. Musical aptitude is associated with AVPR1A-haplotypes. PLoS ONE. 2009;4(5): e5534. doi: 10.1371/journal.pone.0005534

14. Staes N., Koski S.E., Helsen P. et al. Chimpanzee sociability is associated with vasopressin (Avpr1a) but not oxytocin receptor gene (OXTR) variation. Horm Behav. 2015;75:84-90. doi: 10.1016/j.yhbeh.2015.08.006

15. Mulholland M.M., Navabpour S.V., Mareno M.C. et al. AVPR1A variation is linked to gray matter covariation in the social brain network of chimpanzees. Genes Brain Behav. 2020;19(4):e12631. doi: 10.1111/gbb.12631

16. Aluja A., García L.F., García Ó., Blanco E. Testosterone and disinhibited personality in healthy males. Physiol Behav. 2016;164:227-232. doi: 10.1016/j.physbeh.2016.06.007

17. Van den Akker A.L., Briley D.A., Grotzinger A.D. et al. Adolescent Big Five personality and pubertal development: pubertal hormone concentrations and self-reported pubertal status. Dev Psychol. 2021;57(1):60-72. doi: 10.1037/dev0001135

18. Vaeroy H., Schneider F., Fetissov S.O. Neurobiology of aggressive behavior-role of autoantibodies reactive with stress-related peptide hormones. Front Psychiatry. 2019;10:872. doi: 10.3389/fpsyt.2019.00872

19. Федорова С.А. Генетические портреты народов Республики Саха (Якутия): анализ линий митохондриальной ДНК и Y-хромосомы. Якутск: Изд. ЯНЦ СО РАН. 2008; 235 с.

20. Fedorova S.A., Reidla M., Metspalu E. et al. Autosomal and uniparental portraits of the native populations of Sakha (Yakutia): implications for the peopling of Northeast Eurasia. BMC evolutionary biology. 2013; 13:127. doi: 10.1186/1471-2148-13-127

21. Morley A.P., Narayanan M., Mines R. et al. AVPR1A and SLC6A4 polymorphisms in choral singers and non-musicians: A Gene Association Study. PLoS ONE. 2012;7(2): e31763. doi: 10.1371/journal.pone.0031763

22. Алмаев Н.А., Островская Л.Д. Адаптация опросника темперамента и характера Р. Клонинджера на русскоязычной выборке. Психологический журнал. 2005;26(6):77-86.

23. Bielsky I.F., Hu S.B., Szegda K.L. et al. Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice. Neuropsychopharmacology. 2004;29(3):483-493. doi: 10.1038/sj.npp.1300360

24. Inoue-Murayama M., Yokoyama C., Yamanashi Y. et al.Common marmoset (Callithrix jacchus) personality, subjective well-being, hair cortisol level and AVPR1a, OPRM1, and DAT genotypes. Sci Rep. 2018;8(1):10255. doi: 10.1038/s41598-018-28112-7

25. Nishina K., Takagishi H., Takahashi H. et al. Association of Polymorphism of Arginine-Vasopressin Receptor 1A (AVPR1a) Gene With Trust and Reciprocity. Front Hum Neurosci. 2019;13:230. doi: 10.3389/fnhum.2019.00230

26. Brunner J., Keck M.E., Landgraf R. et al. Vasopressin in CSF and plasma in depressed suicide attempters: preliminary results. Eur. Neuropsychopharmacol. 2002;12(5):489-494. doi: 10.1016/s0924-977x(02)00071-8

27. de Winter R.F., van Hemert A.M., Derijk R.H. et al. Anxiousretarded depression: relation with plasma vasopressin and cortisol. Neuropsychopharmacology. 2003;28(1):140-147. doi: 10.1038/sj.npp.1300002

28. Piskunov A., Fusté A., Teryaeva N. et al. The hypothalamic-pituitary-thyroid axis and personality in a sample of healthy subjects. Psychoneuroendocrinology. 2018;87:181-187. doi: 10.1016/j.psyneuen.2017.10.023

29. Arqué J.M., Segura R., Torrubia R. Correlation of thyroxine and thyroid-stimulating hormone with personality measurements: a study in psychosomatic patients and healthy subjects. Neuropsychobiology. 1987;18(3):127-33. doi: 10.1159/000118406

30. Rawal R., Teumer A., Völzke H. et al. Meta-analysis of two genome-wide association studies identifies four genetic loci associated with thyroid function. Hum Mol Genet. 2012;21(14):3275-3282. doi: 10.1093/hmg/dds136

31. Marcisz C., Jonderko G., Kucharz E.J. Changes of plasma arginine-vasopressin level in patients with hyperthyroidism during treatment. Med Sci Monit. 2001;7(3):409-414.

32. Levie D., Korevaar T., Bath S.C. et al. Thyroid function in early pregnancy, child IQ, and autistic traits: a meta-analysis of individual participant data. J Clin Endocrinol Metab. 2018;103(8):2967-2979. doi: 10.1210/jc.2018-00224

33. Aluja A., Torrubia R. Hostility-aggressiveness, sensation seeking, and sex hormones in men: re-exploring their relationship. Neuropsychobiology. 2004;50(1):P.102-107. doi: 10.1159/000077947

34. Markianos M., Tripodianakis J., Istikoglou C. et al. Suicide attempt by jumping: a study of gonadal axis hormones in male suicide attempters versus men who fell by accident. Psychiatry Res. 2009;170(1):82-85. doi: 10.1016/j.psychres.2008.08.001

35. Fischer S., Ehlert U., Amiel Castro R. Hormones of the hypothalamic-pituitary-gonadal (HPG) axis in male depressive disorders - A systematic review and meta-analysis. Front Neuroendocrinol. 2019; 55:100792. doi: 10.1016/j.yfrne.2019.100792

36. Butovskaya M., Rostovtseva V., Butovskaya P. et al. Oxytocin receptor gene polymorphism (rs53576) and digit ratio associates with aggression: comparison in seven ethnic groups. J Physiol Anthropol. 2020;39(1):20. doi: 10.1186/s40101-020-00232-y

37. Hampson E., Ellis C.L., Tenk C.M. On the relation between 2D:4D and sex-dimorphic personality traits. Arch Sex Behav. 2008;37(1):133-144. doi: 10.1007/s10508-007-9263-3