Role of toll-like receptors in complications of cardiac surgery for congenital heart defects in children

Abstract

Background. Cardiac surgery in combination with hypothermia, ischaemia and reperfusion leads to an inflammatory response causing postoperative complications. Toll-like receptors are signalling molecules through which some functions of innate immunity can be activated, and polymorphic variants in the TLR-family genes can be predictors of complications after cardiac surgery.Aim. To study the associations of TLR-family genes with infectious and non-infectious complications of cardiac surgery for congenital heart defects.Methods. The study included 89 children (44 girls and 45 boys) with congenital heart defects who underwent cardiac surgery. Complications occurred in 47 children 47 days after cardiac surgery. There were no complications in 42 children. Genotyping was performed by real-time PCR using TaqMan probes.Results. A two-locus model of gene-gene interaction between TLR1 rs5743551 and TLR2 rs3804099 was the best fit, accounting for 4.01% of phenotypic entropy. The TLR2 gene polymorphic variant rs5743708 had the highest predictive potential (2.59%).Conclusion. The development of postoperative complications of cardiac surgical treatment for congenital heart defects can be due to the synergistic effect of the polymorphic variants rs5743551 in the TLR1 gene and rs3804099 in the TLR2 gene. This effect occurs through the features of TLR1 and TLR2 transcription, the subsequent expression of receptors on cells and signalling which activates the synthesis of proinflammatory cytokines and chemokines.Received 25 February 2021. Revised 11 May 2021. Accepted 12 May 2021.Funding: The work is supported by the complex program of fundamental research of the Siberian Branch of the Russian Academy of Sciences (No. 0554-2019-0002).Conflict of interest: The authors declare no conflicts of interests.Contribution of the authorsConception and study design: A.V. Shabaldin, A.V. Ponasenko, A.V. TsepokinaData collection and analysis: A.A. Anikeenko, A.V. Tsepokina, S.A. ShmulevichStatistical analysis: A.V. Shabaldin, A.V. TsepokinaDrafting the article: A.V. Shabaldin, A.V. Tsepokina, A.V. PonasenkoCritical revision of the article: A.V. TsepokinaFinal approval of the version to be published: A.V. Tsepokina, A.A. Anikeenko, S.A. Shmulevich, A.V. Ponasenko, A.V. Shabaldin