IMPACT OF INNATE IMMUNITY GENES IN DEVELOPMENT OF CRITICAL POSTOPERATIVE COMPLICATIONS AFTER CORONARY ARTERY BYPASSES GRAFTING

Introduction. Postoperative critical complications after coronary artery bypass grafting are the result of innate immunity functioning that related with individual features and sometimes genetically determined. The aim: to evaluate the contribution of innate immunity genes polymorphisms in the development of critical postoperative complications of coronary artery bypass grafting. Design and methods: 680 patients with coronary artery disease after coronary artery bypass grafting were involved in the investigation. TREM-1 and TLR genes polymorph loci were genotyped using allele-specifi c real-time PCR. Results. It was found that allele G rs1817537 (OR = 2,94 (95%CI = 1,09-7,92); р = 0,019), allele Т rs2234246 (OR = 3,64 (95%CI = 1,24-10,73); р = 0,0076) and allele Т rs3804277 (OR = 2,94 (95%CI = 1,09-7,92); р = 0,019) of TREM-1 gene are associated with high risk of multiple organ failure while allele C rs3775073 TLR6 (OR = 0,33 (95%CI = 0,15-0,71); р = 0,0045), allele А rs7768162 TREM-1 (OR = 0,46 (95%CI = 0,21-0,98); р = 0,043) and T/T genotype of rs4711668 TREM-1 (OR = 0,22 (95%CI = 0,05-0,97); р = 0,015) are associated with decreased risk. Conclusion. Rare alleles in some polymorphic sites of innate immunity genes demonstrate the importance in multiple organ failure development.

coronary artery disease, multiple organ failure, coronary bypass grafting, innate immunity, TREM-1, TLR

1. Nowbar AN, Howard JP, Finegold JA et al. 2014 global geographic analysis of mortality from ischaemic heart disease by country, age and income: statistics from World Health Organisation and United Nations. International Journal of Cardiology. 2014; 174(2): 293–298.

2. Møller CH, Steinbrüchel DA. Off-pump versus on-pump coronary artery bypass grafting. Current Cardiology Reports Journal. 2014; 16(3):455

3. Plotnikov GP, SHukevich DL, Grigor’ev EV. Abdominal complication in cardiac surgery with cardiopulmonary bypass. Complex problems of cardiovascular diseases = Kompleksnye problemy serdechno-sosudistyh zabolevanij. 2014; 1:75–86. In Russian [ПлотниковГ. П., Шукевич Д. Л., Григорьев Е. В. Абдоминальные осложнения при операциях на сердце с искусственным кровообращением. Комплексные проблемы сердечно-сосудистых заболеваний. 2014, 1:75–86].

4. Hatakeyama N, Matsuda N. Alert cell strategy: mechanisms of infl ammatory response and organ protection. Current Pharmaceutical Design Journal. 2014; 20(36): 5766–5778.

5. Bone RС. American College of Chest Physicians / Society of Critical Care Medicine Consensus Conference Committee: American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference. Defi nitions for sepsis and multiple organ failure and guidelines for the use of innovative therapies in sepsis. Critical Care Medicine. 1992; 20: 864–874.

6. Scott MC. Defi ning and Diagnosing Sepsis. Emergency Medicine Clinics of North America. 2017; 35 (1): 1–9.

7. Iwasaki A, Medzhitov R. Control of adaptive immunity by the innate immune system. Nature Immunology. 2015; 16 (4): 343–353.

8. Pothlichet J, Quintana-Murci L. The genetics of innate immunity sensors and human disease. International Reviews of Immunology. 2013; 32 (2): 157–208.

9. Vincent J-L, Moreno R, Takala J et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Medicine. 1996; 22 (7): 707–710.

10. Smith К, Kliko С, Cantor C. Puls-elektroforez and methods of work with the big molecules of DNA. The Analysis of the genome. Methods: the Lane with English М: World, 1990. 58–94.

11. Hutornaya MV, Ponasenko AV, Golovkin AS. Triggering receptor expressed on myeloid cells (tremg1): genetic polymorphisms and a role in the immune responses. Medicine in Kuzbass = Medicina v Kuzbasse. 2013; 4(12):14–18. In Russian [Хуторная М. В., Понасенко А. В., Головкин А. С. Триггерный рецептор экспрессируемый на миелоидных клетках (TREM-1): генетический полиморфизм и роль в реализации иммунного ответа. Медицина в Кузбассе. 2013, 4 (12): 14–18].

12. Velez DR, Fortunato SJ, Thorsen P et al. Preterm birth in Caucasians is associated with coagulation and infl ammation pathway gene variants. PLoS One. 2008; 3(9):e3283.

13. Jung ES, Kim SW, Moon CM et al. Relationships between genetic polymorphisms of triggering receptor expressed on myeloid cells-1 and infl ammatory bowel diseases in the Korean population. Life Sci. 2011; 89 (9–10):289–294.

14. Rivera-Chávez FA, Huebinger RM, Burris A et al. A TREM-1 Polymorphism A/T within the Exon 2 Is Associated with Pneumonia in Burn-Injured Patients. ISRN Infl amm. 2013; 2013: 431739.

15. Replogle JM, Chan G, White CC et al. A TREM1 variant alters the accumulation of Alzheimerrelated amyloid pathology. Ann Neurol. 2015; 77 (3): 469–477.

16. Su L, Liu C, Li C et al. Dynamic Changes in Serum Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) and its Gene Polymorphisms are Associated with Sepsis Prognosis. Infl ammation. 2012; 35: 1833.

17. Peng L-S, Li J, Zhou G-S, Deng L-H et al. Relationships between genetic polymorphisms of triggering receptor expressed on myeloid cells-1 and septic shock in a Chinese Han population. World Journal of Emergency Medicine. 2015; 2 (6): 123–130.

18. Chen Q, Zhou H, Wu S, et al. Lack of association between TREM-1 gene polymorphisms and severe sepsis in a Chinese Han population. Hum Immunol. 2008; 69 (3): 220–226.

19. Ponasenko AV, Kutikhin AG, Khutornaya MV et al. Polymorphisms within innate immune response, calcium metabolism and lipid metabolism are predictors of infective endocarditis. Infection and immunity = Infektsiya i immunitet. 2015; 4 (5): 331–338. In Russian [Понасенко А. В., Кутихин А. Г., Хуторная М. В. и др. Связь полиморфизмов гена TREM-1 с инфекционным эндокардитом. Инфекция и иммунитет. 2015, 4 (5): 331–338].

20. Ponasenko AV, Golovkin AS, Khutornaya MV et al. Association of TREM-gene polymorphisms with the risk of the coronary artery disease in russian population. Molecular medicine = Molekulyarnaya medicina. 2017; 1 (15): 34–39. In Russian [Понасенко А. В., Головкин А. С., Хуторная М. В. и др. Связь полиморфизмов гена TREM-1 с риском развития ишемической болезни сердца в русской популяции. Молекулярная медицина. 2017, 1 (15): 34–39].

21. Xie X, Shi X, Liu M. The Roles of TLR Gene Polymorphisms in Atherosclerosis: A Systematic Review and Meta-Analysis of 35,317 Subjects. Scand J Immunol. 2017; 86 (1): 50–58.

22. den Dekker WK, Cheng C, Pasterkamp G, Duckers HJ. Toll like receptor 4 in atherosclerosis and plaque destabilization. Atherosclerosis. 2010; 209(2):314–320.

23. Vallejo JG. Role of Toll-like receptors in cardiovascular diseases. Clin Sci (Lond). 2011; 121 (1): 1–10.

24. Ponasenko AV, Khutornaya MV, Kutikhin AG et al. The role of polymorphisms within genes encoding toll-like receptors in coronary atherosclerosis. Ateroskleroz. 2015; 3(11):22–28. In Russian [Понасенко А. В., Хуторная М. В., Кутихин А. Г. и др. Роль полиморфизмов генов семейства Toll-подобных рецепторов в атеросклеротическом поражении сосудов сердца. Атеросклероз. 2015, 3 (11): 22–28].