Preview

Ateroscleroz

Advanced search

Association of variant of the nucleotide sequence rs1799864 (V64I) of the CCR2 gene and depression, as a risk factor for atherosclerosis-related cardiovascular diseases, among men aged 25–64 years (WHO international MONICA-MOPSY programme)

https://doi.org/10.52727/2078-256X-2026-22-1-20-27

Abstract

Objective – to determine associations between variant nucleotide sequence of rs1799864 (V64I) the CCR2 gene and depression, a risk factor for atherosclerosis-related cardiovascular diseases, among men aged 25–64 in Novosibirsk. Material and methods. This study was conducted in 1994–1995 as part of the WHO MONICA-MOPSY program. A representative sample of men aged 25–64 living in the Oktyabrsky district of Novosibirsk was examined (n = 657 men, mean age 44.3 ± 0.4 years, response rate 82.1 %). The MOPSY depression scale was administered to assess depression. Genotyping of the studied nucleotide sequence variant rs1799864 (V64I) of the CCR2 gene was performed using polymerase chain reaction (PCR). Results. The prevalence of depression among men in the population was 29 %, with 3.1 % having high depression and 25.9 % having moderate depression. The most common genotype of the CCR2 gene was GG, occurring in 78.8 % of men in representative sample, the GA genotype in 19 %, and the AA genotype in 2.2 %. The G allele was found in 88.3 % of men, and the A allele in 11.7 %. Among men with depression, the GA (47.6 %) and AA (2.9 %) genotypes of the CCR2 gene were more common than among men without depression (2.4 % and 1.7 %, respectively). In contrast, among men without depression, the homozygous GG genotype of rs1799864 the CCR2 gene was most common, with 95.9 % of men (p < 0.0001). Among men with depression, the A allele (26.8 %) was observed more often than among individuals without depression – 2.9 % (p < 0.0001). Comparative analysis showed that the incidence of depression was higher among carriers of the GA genotype (49.1 %) and GA+AA (50.6 %) than among men of the GG genotype (2.4 %) (all p < 0.0001). Conclusions. We found that the incidence of depression was higher among carriers of the GA genotype of rs1799864 the CCR2 gene (49.1 %) than among carriers of other genotypes.

About the Authors

V. V. Gafarov
Research Institute for Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation

Valery V. Gafarov, doctor of medical sciences, professor, head laboratory of psychological and sociological problems of therapeutic diseases

175/1, Boris Bogatkov st., Novosibirsk, 630089 



E. A. Gromova
Research Institute for Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation

Elena A. Gromova, doctor of medical sciences, leading researcher laboratory of psychological and sociological problems of therapeutic diseases

175/1, Boris Bogatkov st., Novosibirsk, 630089 



I. V. Gagulin
Research Institute for Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation

Igor V. Gagulin, senior researcher at the laboratory of psychological and sociological problems of therapeutic diseases 

175/1, Boris Bogatkov st., Novosibirsk, 630089 



V. N. Maksimov
Research Institute for Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation

Vladimir N. Maksimov, doctor of medical sciences, professor, head of the laboratory of molecular genetical research 

175/1, Boris Bogatkov st., Novosibirsk, 630089 



A. V. Gafarova
Research Institute for Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation

Almira V. Gafarova, senior researcher at the laboratory of psychological and sociological problems of therapeutic diseases 

175/1, Boris Bogatkov st., Novosibirsk, 630089 



References

1. Pandey G.N., Rizavi H.S., Bhaumik R., Zhang H. Chemokines gene expression in the prefrontal cortex of depressed suicide victims and normal control subjects. Brain, Behavior, and Immun. 2021; 94: 266–273. doi: 10.1016/j.bbi.2021.01.033

2. Rollins B.J. Monocyte chemoattractant protein 1: a potential regulator of monocyte recruitment in inflammatory disease. Mol. Med. Today. 1996; 2 (5): 198–204. doi: 10.1016/1357-4310(96)88772-7

3. Wu X.B., Jing P.B., Zhang Z.J., Cao D.L., Gao M.H., Jiang B.C., Gao Y.-J. Chemokine receptor CCR2 contributes to neuropathic pain and the associated depression via increasing NR2B-mediated currents in both D1 and D2 dopamine receptor-containing medium spiny neurons in the nucleus accumbens shell. Neuropsychopharmacology. 2018; 43 (11): 2320–2330. doi: 10.1038/s41386-018-0115-8

4. Pawlik K., Ciapała K., Ciechanowska A., Kwiatkowski K., Mika J. Pharmacological Evidence of the Important Roles of CCR1 and CCR3 and Their Endogenous Ligands CCL2/7/8 in Hypersensitivity Based on a Murine Model of Neuropathic Pain. Cells. 2022; 12 (1): 98. doi: 10.3390/cells12010098

5. Zhang Z.J., Jiang B.C., Gao Y.-J. Chemokines in neuronglial cell interaction and pathogenesis of neuropathic pain. Cell. Mol. Life Sci. 2017; 74 (18): 3275–3291. doi: 10.1007/s00018-017-2513-1

6. Leighton S.P., Nerurkar L., Krishnadas R., Johnman C., Graham G.J., Cavanagh J. Chemokines in depression in healthand in inflammatory illness: a systematic review and meta-analysis. Mol. Psych. 2018; 23 (1): 48–58. doi: 10.1038/mp.2017.205

7. Gao Y.-J., Zhang L., Samad O.A., Suter M.R., Kawasaki Yasuhiko, Zhen-Zhong Xu, Jong-Yeon Park, Anne-Li Lind, Qiufu Ma, and Ru-Rong Ji. JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain. J. Neurosci. 2009; 29: 4096–4108. doi: 10.1523/JNEUROSCI.3623-08.2009

8. Guyon A., Skrzydelski D., Giry D., Rovère C,. Conductier G., Trocello J.M, Daugé V., Kitabgi P., Rostène W., Nahon J.L., Parsadaniantz S.M.. Long term exposure to the chemokine CCL2 activates the nigrostriatal dopamine system: a novel mechanism for the control of dopamine release. Neuroscience. 2009; 162: 1072–1080. doi:10.1016/j.neuroscience.2009.05.048

9. Wakida N., Kiguchi N., Saika F., Nishiue H., Kobayashi Y., Kishioka S. CC-chemokine ligand 2 facilitates conditioned place preference to methamphetamine through the activation of dopamine systems. J. Pharmacol. Sci. 2014; 125: 68–73. doi: 10.1254/jphs.14032FP

10. Lim B.K., Huang K.W., Grueter B.A., Rothwell P.E., Malenka R.C. Anhedonia requires MC4R-mediated synaptic adaptations in nucleus accumbens. Nature. 2012; 487: 183–189. doi: 10.1038/nature11160

11. Ngoufack M.N., Nkenfou C.N., Tiedeu B.A., NguefackTsague G., Mouafo L.C.M., Dambaya B., Nguefeu C.N., Ndzi E.N., Billong S.C., Mbacham W.F., Ndjolo A. CCR2 polymorphism and HIV: mutation in both mother and child is associated with higher transmission. Int. J. Biochem. Mol. Biol. 2019; 10 (4): 42–48.

12. Colotto M., Rubini G., Savoriti C., D’Adduogo N., Mercuri S. Impact of depression syndrome in the management of cardiovascular risk factors in primary prevention: State of the art. Clin. Ter. 2010; 161 (3): 105–110.

13. van der Kooy K., van Hout H., Marwijk H., Marten H., Stehouwer C., Beekman A. Depression and the risk for cardiovascular diseases: systematic review and meta analysis. Int. J. Geriatr. Psych. 2007; 22 (7): 613–626.

14. González P., Alvarez R., Batalla A., Reguero J.R., Alvarez V., Astudillo A., Cubero G.I., Cortina A., Coto E. Genetic variation at the chemokine receptors CCR5/CCR2 in myocardial infarction. Genes Immun. 2001, Jun; 2 (4): 191–195. doi: 10.1038/sj.gene.6363760

15. Bühl A., Zöfel P. SPSS, Version 10. Einführung in die moderne Datenanalyse unter Windows, 2005. 608 p.

16. Institute for Health Metrics and Evaluation (IHME) GBD Compare Data Visualization Seattle. IHME, University of Washington: WA, 2016. Available from http://vizhub.healthdata.org/gbd-compare

17. Song J., Ma Z., Zhang H., Liang T., Zhang J. Identification of novel biomarkers linking depressive disorder and Alzheimer’s disease based on an integrative bioinformatics analysis. BMC Genom Data. 2023; 24 (1): 22. doi: 10.1186/s12863-023-01120-x

18. Goldsmith D.R., Rapaport M.H., Miller B.J. A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia bipolar disorder and depression. Mol. Psych. 2016; 21 (12): 1696–1709. doi: 10.1038/mp.2016.3

19. Bhattacharya A., Drevets W.C. Role of Neuro-Immunological Factors in the Pathophysiology of Mood Disorders: Implications for Novel Therapeutics for Treatment Resistant Depression. Curr. Top. Behav. Neurosci. 2017; 31: 339–356. doi: 10.1007/7854_2016_43 PMID: 27677784

20. Maksimova N.M., Rusyaev V.Yu., Uzbekov M.G. Neurobiological mechanisms of development of resistant depressions. Soc. and Clin. Psych. 2021; 31 (4): 71–79. (In Russ.).

21. Eyre H., Air T., Proctor S., Rositano S., Baune B.T. A critical review of the efficacy of non-steroidal anti-inflammatory drugs in depression. Prog. Neuro-Psychopharmacol. Biol. Psych. 2015; 57: 11–16. doi: 10.1016/j.pnpbp.2014.10.003

22. Ransohoff R.M., Brown M.A. Innate immunity in the central nervous system. J. Clin. Invest. 2012; 122: 1164–1171.

23. Stuart M.J., Baune B.T. Chemokines and chemokine receptors in mood disorders, schizophrenia, and cognitive impairment: a systematic review of biomarker studies. Neurosci. Biobehav. Rev. 2014; 42: 93–115.

24. Stuart M.J., Singhal G., Baune B.T. Systematic review of the neurobiological relevance of chemokines to psychiatric disorders. Front. Cell. Neurosci. 2015; 9: 357.

25. Reaux-Le Goazigo A., van Steenwinckel J., Rostene W., Melik Parsadaniantz S. Current status of chemokines in the adult CNS. Prog. Neurobiol. 2013; 104: 67–92.

26. Eyre H.A., Air T., Pradhan A., Johnston J., Lavretsky H., Stuart M.J., Baune B.T. A meta-analysis of chemokines in major depression. Prog. Neuropsychopharmacol. Biol. Psych. 2016, Jul 4; 68: 1–8. doi: 10.1016/j.pnpbp.2016.02.006

27. Amarjargal Ya., Rudko A.A. Polymorphism of the CCR5, CCR2, and SDF1 genes in the Mongolian population. Med. Genetika. 2007; 5: 30–33. (In Russ.).

28. Voevoda M.I., Ustinov S.N., Yudin N.S., Dolgikh M.M., Kuznetsova T.N., Maksimov V.N., Kulikov I.V., Gromov A.A., Shabalin A.V., Semaeva E.V., Kobzev V.F., Baum S.R., Gafarov V.V., Malyutina S.K., Romashchenko A.G., Nikitin Yu.P. Association of polymorphism of the CCR2 chemokine receptor gene with myocardial infarction. Dokl. AS. 2002; 385 (2): 367–370. (In Russ.).

29. Proma M.A., Daria S., Nahar Z., Ashraful Islam S.M., Bhuiyan M.A., Islam M.R. Monocyte Chemoattractant Protein-1 Levels Are Associated with Major Depressive Disorder. J. Basic Clin. Physiol. Pharm. 2022; 33: 735–741. doi: 10.1515/jbcpp-2021-0132

30. Myung W., Lim S.-W., Woo H.I., Park J.H., Shim S., Lee S.-Y., Kim D.K. Serum Cytokine Levels in Major Depressive Disorder and Its Role in Antidepressant Response. Psych. Investig. 2016; 13: 644–651. doi: 10.4306/pi.2016.13.6.644

31. Janelidze S., Ventorp F., Erhardt S., Hansson O., Minthon L., Flax J., Samuelsson M., Traskman-Bendz L., Brundin L. Altered Chemokine Levels in the Cerebrospinal Fluid and Plasma of Suicide Attempters. Psychoneuroendocrinology. 2013; 38: 853–862. doi: 10.1016/j.psyneuen.2012.09.010

32. Simon N.M., McNamara K., Chow C.W., Maser R.S., Papakostas G.I., Pollack M.H., Nierenberg A.A., Fava M., Wong K.K. A Detailed Examination of Cytokine Abnormalities in Major Depressive Disorder. Eur. Neuropsychopharmacol. 2008; 18: 230–233. doi: 10.1016/j.euroneuro.2007.06.004

33. Zhou Z., Guille C., Ogunrinde E., Liu R., Luo Z., Powell A., Jiang W. Increased Systemic Microbial Translocation Is Associated with Depression during Early Pregnancy. J. Psychiatr. Res. 2018; 97: 54–57. doi: 10.1016/j.jpsychires.2017.11.009

34. Curzytek K., Leśkiewicz M. Targeting the CCL2-CCR2 Axis in Depressive Disorders. Pharm. Rep. 2021; 73: 1052–1062. doi: 10.1007/s43440-021-00280-w

35. Harsanyi S., Kupcova I., Danisovic L., Klein M. Selected Biomarkers of Depression: What Are the Effects of Cytokines and Inflammation? Int. J. Mol. Sci. 2022; 24 (1): 578. doi: 10.3390/ijms24010578


Review

For citations:


Gafarov V.V., Gromova E.A., Gagulin I.V., Maksimov V.N., Gafarova A.V. Association of variant of the nucleotide sequence rs1799864 (V64I) of the CCR2 gene and depression, as a risk factor for atherosclerosis-related cardiovascular diseases, among men aged 25–64 years (WHO international MONICA-MOPSY programme). Ateroscleroz. 2026;22(1):20-27. (In Russ.) https://doi.org/10.52727/2078-256X-2026-22-1-20-27

Views: 144

JATS XML


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2078-256X (Print)
ISSN 2949-3633 (Online)