Genetic predisposition to alcoholism, schizophrenia and Alzheimer’s disease with psychodiagnostic characteristics in russian population
https://doi.org/10.20538/1682-0363-2016-5-83-96
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Abstract
The purpose of this paper is to identify genetic factors connected with personal features using the panel of 12 polymorphic markers associated with the risk of developing dementia in patients with Alzheimer’s disease, schizophrenia and alcoholism.
Materials and methods. The correlation among quantitative traits of personality, temperament and character determined with Cattell’s (the Sixteen personality factor questionnaire (16PF)), Leonhard-Schmieschek’s, Spielberger-Khanin’s, and Eysenck’s (IQ) tests were analyzed with polymorphic variants of 12 genes involved in the development of severe mental disorders such as alcoholism, schizophrenia and Alzheimer’s disease. DNA samples of 150 students were genotyped using PCR-RPLF method. The data were processed by nonparametric statistical methods.
Results. Interallelic nonrandom associations in paired combinations of GABRA2-PICALM, PICALMADCY3, CLU-CBX7 and CLU-ADCY3 polymorphisms were detected. This may indicate the adaptive selection influencing the maintenance of behavioral homeostasis in population. A number of statistically significant associations of genetic variation were found: CLU with perfectionism(Q3) of 16PF and the exaltation of the Leonhard’s tests, PICALM with tension (Q4) of 16PF and the imbalance of Leonhard’s tests, DISC1 with vigilance(L) of 16PF, and exaltation, cyclothymia of Leonhard’s tests, ZNF804A with imbalance by Leonhard’s test, SLC6A4 with reasoning(B) of 16PF test, ADCY3 with self-reliance(Q2) and extraversion(F2) of 16PF test, MIR9-2 emotional stability(C), liveliness(F), social boldness(H), extraversion(F2) of 16PF, and dysthymia, hyperthymia of Leonhard’s tests, with the personal anxiety of Spielberger-Khanin’s test, CBX7 with vigilance(L), warmth(A) of 16PF test, SLC6A3 with IQ.
Conclusion. These findings support the idea of overlapping genetic component in common mental and neurological disorders and variability of human cognitive and personality traits.
About the Authors
A. V. Marusin
The Research Institute for Medical Genetics, National Research Medical Center (TNRMC), Russian Academy of Sciences (RAS)
Russian Federation
Russian Federation
PhD, Scientific Researcher of Laboratory for Evolutionary Genetics,
10, Nab. Ushaiki, Tomsk, 634050
A. N. Kornetov
Siberian State Medical University
Russian Federation
Russian Federation
MD, Academic Dean of the Faculty of Behavioral Medicine and Management, Head of Department of Clinical Psychology and Psychotherapy,
2, Moscow Trakt, Tomsk, 634055
M. G. Swarovskaya
The Research Institute for Medical Genetics, National Research Medical Center (TNRMC), Russian Academy of Sciences (RAS)
Russian Federation
Russian Federation
PhD, Scientific Researcher of Laboratory for Evolutionary Genetics, Research Institute for Medical Genetics,
10, Nab. Ushaiki, Tomsk, 634050
K. V. Vagaitseva
The Research Institute for Medical Genetics, National Research Medical Center (TNRMC), Russian Academy of Sciences (RAS);
National Research Tomsk State University
Russian Federation
Russian Federation
PhD, Scientific Researcher of Laboratory for Evolutionary Genetics, Research Institute for Medical Genetics, 10, Nab. Ushaiki, Tomsk, 634050;
Scientific Researcher of Laboratory for Human Onthogenetics, 36, Lenin Av., Tomsk, 634050
E. S. Pavlenyuk
Siberian State Medical University
Russian Federation
Russian Federation
Student of Department of Clinical Psychology, Psychotherapy,
2, Moscow Trakt, Tomsk, 634055
V. A. Stepanov
The Research Institute for Medical Genetics, National Research Medical Center (TNRMC), Russian Academy of Sciences (RAS);
National Research Tomsk State University
Russian Federation
Russian Federation
MD, Professor, Corresponding Member of the Russian Academy of Sciences, Head of Laboratory for Evolutionary Genetics, Research Institute for Medical Genetics,
10, Nab. Ushaiki, Tomsk, 634050;
Head of Laboratory for Human Onthogenetics, 36, Lenin Av., Tomsk, 634050
References
1. Livesley W.J., Jang K.L. The behavioral genetics of personality disorder // Annu Rev. Clin. Psychol. 2008; 4: 247-274.
2. Bouchard T.J.Jr., Loehlin J.C. Genes, evolution, and personality // Behav. Genet. 2001; May, 31 (3): 243-273.
3. Lind P.A., Macgregor S., Agrawal A. et al. The role of GABRA2 in alcohol dependence, smoking, and illicit drug use in an Australian population sample // Alcohol. Clin. Exp. Res. 2008; Oct., 32 (10): 1721-1731. https://doi.org/10.1111/j.1530-0277.2008.00768.x. Epub 2008 Aug 22.
4. Philibert R.A., Gunter T.D., Beach S.R. et al. Role of GABRA2 on risk for alcohol, nicotine, and cannabis dependence in the Iowa Adoption Studies // Psychiatr. Genet. 2009; Apr., 19 (2): 91-98. https://doi.org/10.1097/YPG.0b013e3283208026.
5. Lee J.H., Cheng R., Barral S. et al. Identification of novel loci for Alzheimer disease and replication of CLU, PICALM, and BIN1 in Caribbean Hispanic individuals // Arch. Neurol. 2011 Mar., 68 (3): 320-328. https://doi.org/10.1001/archneurol.2010.292. Epub 2010 Nov 8.
6. Golenkina S.A., Gol’cov A.Yu., Kuznecova I.L. i dr. Polimorfizm gena klasterina (CLU/APOJ) pri bolezni Al’cgejmera i v norme v rossijskih populyaciyah [Analysis of clusterin gene (CLU/APOJ) polymorphism in Alzheimer’s disease patients and in normal cohorts from Russian populations] // Molekulyarnaya Biologiya - Molecular Biology, 2010; 44 (4): 620-626 (in Russian).
7. Donohoe G., Rose E., Frodl T. et al. ZNF804A risk allele is associated with relatively intact gray matter volume in patients with schizophrenia // Neuroimage. 2011; Feb. 1; 54 (3): 2132-2137. https://doi.org/10.1016/j.neuroimage.2010.09.089.Epub 2010 Oct 8.
8. URL=http://atlasgeneticsoncology.org/Genes/CBX7ID-43845ch22q13.html
9. Leliveld S.R., Bader V., Hendriks P. et al. Insolubility of disrupted-in-schizophrenia 1 disrupts oligomer-dependent interactions with nuclear distribution element 1 and is associated with sporadic mental disease // J. Neurosci. 2008; Apr. 9, 28 (15): 3839-3845. https://doi.org/10.1523/JNEUROSCI.5389-07.2008.
10. Maeda K., Nwulia E., Chang J. et al. Differential expression of disrupted-in-schizophrenia (DISC1) in bipolar disorder // Biol. Psychiatry. 2006; Nov. 1, 60 (9): 929-935.
11. Sawamura N., Sawamura-Yamamoto T., Ozeki Y. et al. A form of DISC1 enriched in nucleus: altered subcellular distribution in orbitofrontal cortex in psychosis and substance/alcohol abuse // Proc. Natl. Acad. Sci. USA. 2005; Jan. 25, 102 (4): 1187-1192.
12. Ikram M.A., Liu F., Oostra B.A. et al. The GAB2 gene and the risk of Alzheimer’s disease: replication and meta-analysis // Biol. Psychiatry. 2009; Jun. 1, 65 (11): 995-999. https://doi.org/10.1016/j.biopsych.2008.11.014. Epub 2008 Dec 31.
13. Cheunsuk S., Hsu T., Gershwin M.E., Bowlus C.L. Analysis of the IDDM candidate gene Prss16 in NOD and NON mice // Dev. Immunol. 2002; Dec., 9 (4): 183-186.
14. Lie B.A., Akselsen H.E., Bowlus C.L. et al. Polymorphisms in the gene encoding thymus-specific serine protease in the extended HLA complex: a potential candidate gene for autoimmune and HLA-associated diseases // Genes. Immun. 2002; Aug., 3 (5): 306-312.
15. Shi J., Levinson D.F., Duan J. et al. Common variants on chromosome 6p22.1 are associated with schizophrenia // Nature. 2009; Aug., 6, 460 (7256): 753-757. https://doi.org/10.1038/nature08192. Epub 2009 Jul 1.
16. Edenberg H.J., Koller D.L., Xuei X. et al. Genome-wide association study of alcohol dependence implicates a region on chromosome 11 // Alcohol. Clin. Exp. Res. 2010; May, 34 (5): 840-852. https://doi.org/10.1111/j.1530-0277.2010.01156.x. Epub 2010 Mar 1.
17. Nordman S., Abulaiti A., Hilding A. Genetic variation of the adenylyl cyclase 3 (AC3) locus and its influence on type 2 diabetes and obesity susceptibility in Swedish men // Int. J. Obes. (Lond). 2008; Mar., 32 (3): 407-412.
18. Wray N.R., Pergadia M.L., Blackwood D.H. et al. Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned // Mol. Psychiatry. 2012; Jan., 17 (1): 36-48. https://doi.org/10.1038/mp.2010.109. Epub 2010 Nov 2.
19. Rodriguez-Otero P., Roman-Gomez J., Vilas-Zornoza A. et al. Deregulation of FGFR1 and CDK6 oncogenic pathways in acute lymphoblastic leukaemia harbouring epigenetic modifications of the MIR9 family // Br. J. Haematol. 2011; Oct., 155 (1): 73-83. https://doi.org/10.1111/j.1365-2141.2011.08812.x. Epub 2011 Aug 2.
20. Hauberg M.E., Roussos P., Grove J., Borglum A.D., Mattheisen M.; Schizophrenia Working Group of the Psychiatric Genomics Consortium. Analyzing the Role of MicroRNAs in Schizophrenia in the Context of Common Genetic Risk Variants // JAMA Psychiatry. 2016; Apr. 1, 73 (4): 369-377. https://doi.org/10.1001/jamapsychiatry.2015.3018.
21. Bligh-Glover W., Kolli T.N., Shapiro-Kulnane L. et al. The serotonin transporter in the midbrain of suicide victims with major depression // Biol. Psychiatry. 2000; Jun. 15, 47 (12): 1015-1024.
22. Gonda X., Fountoulakis K.N., Juhasz G. et al. Association of the s allele of the 5-HTTLPR with neuroticism-related traits and temperaments in a psychiatrically healthy population // Eur. Arch. Psychiatry Clin. Neurosci. 2009; Mar., 259 (2): 106-113. https://doi.org/10.1007/s00406-008-0842-7. Epub 2008 Sep 19.
23. Haberstick B.C., Smolen A., Hewitt J.K. Family-based association test of the 5HTTLPR and aggressive behavior in a general population sample of children // Biol. Psychiatry. 2006; May 1, 59 (9): 836-843.
24. Hammoumi S., Payen A., Favre J.D. et al. Does the short variant of the serotonin transporter linked polymorphic region constitute a marker of alcohol dependence? // Alcohol. 1999; Feb., 17 (2): 107-112.
25. Persico A.M., Militerni R., Bravaccio C. et al. Lack of association between serotonin transporter gene promoter variants and autistic disorder in two ethnically distinct samples // Am. J. Med. Genet. 2000; Feb., 96 (1): 123-127.
26. Dougherty D.D., Bonab A.A., Spencer T.J. et al. Dopamine transporter density in patients with attention deficit hyperactivity disorder // Lancet. 1999; Dec., 354 (9196): 2132-2133.
27. Lerman C., Shields P.G., Wileyto E.P. et al. Effects of dopamine transporter and receptor polymorphisms on smoking cessation in a bupropion clinical trial // Health Psychol. 2003; Sep., 22 (5): 541-548.
28. Lohoff F.W., Bloch P.J., Hodge R. et al. Association analysis between polymorphisms in the dopamine D2 receptor (DRD2) and dopamine transporter (DAT1) genes with cocaine dependence // Neurosci. Lett. 2010; Apr., 473 (2): 87-91. https://doi.org/10.1016/j.neulet.2010.02.021. Epub 2010 Feb 17.
29. Sander T., Berlin W., Ostapowicz A. et al. Variation of the genes encoding the human glutamate EAAT2, serotonin and dopamine transporters and Susceptibility to idiopathic generalized epilepsy // Epilepsy Res. 2000; Aug., 41 (1): 75-81.
30. Van der Zwaluw C.S., Engels R.C., Buitelaar J. et al. Polymorphisms in the dopamine transporter gene (SLC6A3/DAT1) and alcohol dependence in humans: a systematic review // Pharmacogenomics. 2009; May, 10 (5): 853-866. https://doi.org/10.2217/pgs.09.24.
31. Sossi V., de la Fuente-Fernandez R., Schulzer M. et al. Dopamine transporter relation to dopamine turnover in Parkinson’s disease: a positron emission tomography study // Ann. Neurol. 2007; Nov., 62 (5): 468-474.
32. Maniatis T., Fritch E.E., Sambrook J. Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, 1982: 545 (Russ ed. Maniatis T., Frich Eh., Sehmbruk Dzh. Metody geneticheskoj inzhenerii. Molekulyarnoe klonirovanie. Moscow: Mir Publ., 1984: 480) (in Russian).
33. Kapustina A.N . Mnogofaktornaya lichnostnaya metodika R. Kettella [Multifactor personal technique R. Cattell]. St. Petersburg: Rech’ Publ., 2004: 104 (in Russian).
34. Cattell R.B., Eber H.W., Tatsuoka M.M. Handbook for the sixteen personality factor questionnaire (16PF). Illinois, 1970: 700.
35. Kortneva Yu. V. Diagnostika aktual’noj problemy. Metodika Leongarda-SHmisheka [Diagnosis of the actual problem. Methods Leonhard-Shmisheka]. Moscow: Institut obshchegumanitarnyh issledovanij Publ., 2004: 240 (in Russian).
36. Batarshev A.V. Bazovye psihologicheskie svojstva i samoopredelenie lichnosti: Prakticheskoe rukovodstvo po psihologicheskoj diagnostike [Basic psychological characteristics and self-identity: A Practical Guide to psychological diagnostics] St. Petersburg: Rech’ Publ., 2005: 44−49 (in Russian).
37. Zhivotovskij L.A. Populyacionnaya biometriya [Population biometrics]. Moscow: Nauka Publ., 1991: 270 (in Russian).
38. Torgersen S. Behavioral genetics of personality // Curr. Psychiatry Rep. 2005. Mar. 7 (1): 51-56.
39. Stepanov V.A., Bocharova A.V., Marusin A.V., Zhukova N.G., Alifirova V.M., Zhukova I.A. Replikativnyj analiz associacij geneticheskih markerov kognitivnyh priznakov s bolezn’ju Al’cgejmera v rossijskoj populjacii [Replicative association analysis of genetic markers of cognitive traits with Alzheimer’s disease in a Russian population] // Molekuljarnaja biologija - Molecular Biology. 2014; 48 (6): 835-844. URL: http://link.springer.com/article/10.1134/S0026893314060168 (accessed 4 May 2016). (in Russian).
40. Stepanov V.A., Bocharova A.V., Saduakassova K.Z., Marusin A.V., Koneva L.A., Vagaitseva K.V., Svyatova G.S. Replikativnoe issledovanie podverzhennosti shizofrenii s rannim nachalom u kazahov [Replicative study of susceptibility to childhoodonset schizophrenia in kazakhs] // Genetika - Russian Journal of Genetics. 2015; 51 (2): 227-235, URL: http://link.springer.com/article/10.1134/S1022795415020143 (accessed 4 May 2016) (in Russian).
41. Pham X., Sun C., Chen X. et al. Association study between GABA receptor genes and anxiety spectrum disorders // Depress. Anxiety. 2009; 26 (11): 998-1003. https://doi.org/10.1002/da.20628.
42. Sapkota S., Wiebe S.A., Small B.J., Dixon R.A. Apolipoprotein E and Clusterin can magnify effects of personality vulnerability on declarative memory performance in non-demented older adults // Int. J. Geriatr. Psychiatry. 2016; May, 31 (5): 502-509. https://doi.org/10.1002/gps.4355. Epub 2015 Sep 7.
43. Marusin A.V., Maksimova N.R., Matveeva N.P. i dr. Associaciya polimorfizma genov perenoschika dofamina DAT1 (SLC6A3) i ehtanol-metaboliziruyushchih fermentov ADH1B i CYP2E1 s riskom formirovaniya alkogol’noj zavisimosti v yakutskoj populyacii [Dopamine transporter DAT1 (SLC6A3) and alcohol metabolizing enzymes ADH1B, CYP2E1 gene polymorphism: association with alcohol dependence in Yakut population] // Yakutskij medicinskij zhurnal - Yakut medical journal. 2009; 2: 148-150. URL: http://ymj.ykt.ru/files/YMJ-2-2009.pdf (accessed 29 April 2016) (in Russian).
44. Golimbet V.E., Alfimova M.V., Shcherbatykh T.V., Rogaev E.I. Gene insertion and deletion polymorphism in the serotonin transporter gene and personality traits measured by MMPI // Genetika. 2003; Apr., 39 (4): 534-539.
45. Hu X., Oroszi G., Chun J. et al. An expanded evaluation of the relationship of four alleles to the level of response to alcohol and the alcoholism risk // Alcohol. Clin. Exp. Res. 2005; Jan., 29 (1): 8-16.
46. Lesch K.P., Bengel D., Heils A. et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region // Science. 1996; Nov., 274 (5292): 1527-1531.
47. VanNess S.H., Owens M.J., Kilts C.D. The variable number of tandem repeats element in DAT1 regulates in vitro dopamine transporter density // BMC Genet. 2005; 6: 55. https://doi.org/10.1186/1471-2156-6-55. URL: http://www.biomedcentral.com/1471-2156/6/55 (accessed 29 April 2016).
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For citations:
Marusin A.V., Kornetov A.N., Swarovskaya M.G., Vagaitseva K.V., Pavlenyuk E.S., Stepanov V.A. Genetic predisposition to alcoholism, schizophrenia and Alzheimer’s disease with psychodiagnostic characteristics in russian population. Bulletin of Siberian Medicine. 2016;15(5):83-96. (In Russ.) https://doi.org/10.20538/1682-0363-2016-5-83-96
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ISSN 1819-3684 (Online)
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