G308A tumor necrosis factor-α gene polymorphism and depression in an open male population aged 25–64 years from Novosibirsk (an epidemiological study according to the WHO MONICA-psychosocial program)

Objective: to investigate the association of G308A tumor necrosis factor-α (TNF-α) (rs1800629) gene polymorphism with depression in an open male population aged 25–64 years in Novosibirsk.

Patients and methods. The investigation was conducted within the framework of the WHO MONICA-psychosocial (Multinational Monitoring of Trends and Determinants of Cardiovascular Disease) program using the material of Screening III of a representative sample of 25–64-yearold men (n=657; mean age, 44.3±0.4 years; response rate, 82.1%) from an open Novosibirsk population in 1994. The depression scale (Mopsy Test) form was used to assess depression. Depression was assessed as none, moderate (MD), or severe (SD).

Results. The prevalence of depression in the 25–64-year-old male population was 29% (MD, 25.9%; SD, 3.1%). There were TNF-α G/G, G/A, and A/A genotypes in 79.1, 19, and 1.9% of cases, respectively. The G allele was present in 88.6% of the men and the A allele was only in 11.4%. Comparative analysis showed that the G/A genotype was more common in men with MD (28.8%) than in those without depression (14.8%): χ2 =6.486; df=1; p=0.011; odds ratio (OR), 2.316; 95% confidence interval (CI), 1.202–4.463. The G/A genotype was also more frequently observed in individuals with depression (MD and SD, 26,5%) than in men without depression (14.8%): χ2 =5.256; df=1; p=0.022; OR, 2.072; 95% CI, 1.103–3.892 compared with G/G genotype carriers. Carriage of the A allele was more often noted in individuals with MD (17.4%) than in those without depression (8%) (χ2 =9.67; df=1; p=0.002; OR=2.43; 95% CI, 1.371–4.307; similarly, A allele carriers were more common among the individuals with MD and SD (163.6%) than among the examinees without depression (8%) (χ2 =9.122; df=1; p=0.003; OR=2.296; 95% CI, 1.325–3.98).

Discussion. Analysis of the association of G308A TNF-α gene polymorphism with depression showed that although the G/G genotype proved to be most frequently found in the G308A TNF-α gene polymorphism, the heterozygous G/A genotype and the homozygous A/A genotype, the A allele were more often detected in depression. Subsequent comparative analysis confirmed that the OR for the development of MD and depression (MD and SD) in individuals with the G/A genotype was increased by 2.3 and 2 times, respectively.

Conclusion. A significant association was found between depression and G308A TNF-α gene polymorphism. 

1. Berg AO, Allan JD, Frame PS, et al. U.S. Preventive Services Task Force. Screening for depression: recommendations and rationale. Ann Intern Med. 2002 May 21;136(10):760-4. doi: 10.7326/0003-4819-136-10-200205210-00012

2. Топчий НВ. Депрессивные расстройства в практике поликлинического врача. Фарматека. 2005;(10):36–41. [Topchiy NV Depressive disorders in the outpatient practice of a physician. Farmateka. 2005;(10):36-41. (In Russ.)].

3. Pariante C, Nemeroff C. Unipolar depression. Handb Clin Neurol. 2012;106:239-49. doi: 10.1016/B978-0-444-52002-9.00014-0.

4. Pigott H, Leventhal A, Alter G, et al. Efficacy and effectiveness of antidepressants: current status of research. Psychother Psychosom. 2010;79(5):267-79. doi: 10.1159/000318293. Epub 2010 Jul 9.

5. Sullivan P, Neale M, Kendler K. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry. 2000 Oct;157(10): 1552-62. doi:10.1176/appi.ajp.157.10.1552

6. Zunszain PA, Anacker C, Cattaneo A, et al. Glucocorticoids, cytokines and brain abnormalities in depression. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Apr 29;35(3):722-9. doi: 10.1016/j.pnpbp.2010.04.011. Epub 2010 Apr 18.

7. Valkanova V, Ebmeier K, Allan C. CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies. J Affect Disord. 2013 Sep 25;150(3):736-44. doi: 10.1016/j.jad.2013.06.004. Epub 2013 Jul 17.

8. Miller A, Raison C. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016 Jan;16(1):22-34. doi: 10.1038/nri.2015.5.

9. Iwata M, Ota K, Duman R. The inflammasome: pathways linking psychological stress, depression, and systemic illnesses. Brain Behav Immun. 2013 Jul;31:105-14. doi: 10.1016/j.bbi. 2012.12.008. Epub 2012 Dec 20.

10. Maslanik T, Mahaffey L, Tannura K, et al. The inflammasome and danger associated molecular patterns (DAMPs) are implicated in cytokine and chemokine responses following stressor exposure. Brain Behav Immun. 2013 Feb;28:54-62. doi: 10.1016/j.bbi.2012.10.014. Epub 2012 Oct 24.

11. Barnes J, Mondelli V, Pariante CM. Genetic Contributions of Inflammation to Depression. Neuropsychopharmacology. 2017 Jan;42(1):81-98. doi: 10.1038/npp.2016.169. Epub 2016 Aug 24.

12. Dowlati Y, Herrmann N, Swardfager W, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010 Mar 1;67(5): 446-57. doi: 10.1016/j.biopsych.2009.09.033. Epub 2009 Dec 16.

13. Postal M, Lapa AT, Sinicato NA, et al. Depressive symptoms are associated with tumor necrosis factor alpha in systemic lupus erythematosus. J Neuroinflammation. 2016 Jan 6;13:5. doi: 10.1186/s12974-015-0471-9.

14. Hajeer AH, Hutchinson IV. Influence of TNF alpha gene polymorphisms on TNF alpha production and disease. Hum Immunol. 2001 Nov;62(11):1191-9.

15. MONICA Monograph and Multimedia Sourcebook. Helsinki; 2003. 237 p.

16. Warzocha K, Ribeiro P, Jacques B, et al. Genetic polymorphisms in the Tumor Necrosis Factor Locus Influence Non-Hodgkin's Lymphoma Outcome. Blood. 1998 May 15;91(10):3574-81.

17. Бююль А, Цёфель П. SPSS: искусство обработки информации. Анализ статистических данных и восстановление скрытых закономерностей. Санкт-Петербург: DiaSoftЮП; 2015. 608 с. [Byuyul' A, Tsefel' P. SPSS: iskusstvo obrabotki informatsii. Analiz statisticheskikh dannykh i vosstanovlenie skrytykh zakonomernostei [SPSS: the art of information processing. The analysis of statistical data and restoration of hidden patterns]. SaintPetersburg: DiaSoftYuP; 2015. 608 p.]

18. Clerici M, Arosio B, Mundo E, et al Cytokine polymorphisms in the pathophysiology of mood disorders. CNS Spectr. 2009 Aug;14(8): 419-25. doi: 10.1017/S1092852900020393

19. Jun TY, Pae CU, Hoon-Han, et al. Possible association between -G308A tumour necrosis factor-alpha gene polymorphism and major depressive disorder in the Korean population. Psychiatr Genet. 2003 Sep;13(3):179-81. doi: 10.1111/j.1365-3083.2011.02602.x

20. Kim JM, Stewart R, Kim SW, et al. Associations of cytokine gene polymorphisms with post-stroke depression. World J Biol Psychiatry. 2012 Dec;13(8):579-87. doi: 10.3109/ 15622975.2011.588247. Epub 2011 Jul 27.