POLYMORPHISMS WITHIN INNATE IMMUNE RESPONSE, CALCIUM METABOLISM AND LIPID METABOLISM ARE PREDICTORS OF INFECTIVE ENDOCARDITIS

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Abstract

Infective endocarditis (IE) is a septic inflammation of the endocardium generally caused by bacteria. Despite certain advances in treatment, case fatality rate and mortality of IE are still relatively high, particularly in high-risk groups. This requires the development of novel efficient preventive approaches; one of them is a personalized medicine. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. We hypothesized that inherited genomic variation in the abovementioned pathways may determine individual susceptibility to IE. Having recruited 124 patients with IE and 300 age-, sex-, and ethnicity-matched healthy controls, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in pathways mentioned above, with the further genetic association analysis. Genotyping was performed using TaqMan allelic discrimination assay while statistical analysis was carried out utilizing SNPStats, a web tool for genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene are associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene is associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1β and IL-12, respectively, suggesting their possible importance for IE development. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE. However, further molecular epidemiology studies are needed to thoroughly uncover the genetic basis of IE.

About the authors

A. V. Ponasenko

Research Institute for Complex Issues of Cardiovascular Diseases

Author for correspondence.
Email: avapanass@mail.ru

PhD (Medicine), Head of the Laboratory of Genomic Medicine, Division of Experimental and Clinical Cardiology,

650002, Kemerovo, Sosnovy avenue, 6

Russian Federation

A. G. Kutikhin

Research Institute for Complex Issues of Cardiovascular Diseases

Email: fake@neicon.ru

PhD (Medicine), Senior Researcher, Laboratory of Genomic Medicine, Division of Experimental and Clinical Cardiology, 

650002, Kemerovo, Sosnovy avenue, 6

Russian Federation

M. V. Khutornaya

Research Institute for Complex Issues of Cardiovascular Diseases

Email: fake@neicon.ru

Junior Researcher, Laboratory of Genomic Medicine, Division of Experimental and Clinical Cardiology,

650002, Kemerovo, Sosnovy avenue, 6

Russian Federation

N. V. Rutkovskaya

Research Institute for Complex Issues of Cardiovascular Diseases

Email: fake@neicon.ru

PhD, MD (Medicine), Senior Researcher, Laboratory of Bioprosthetic Heart Valves, Division of Experimental and Clinical Cardiology,

650002, Kemerovo, Sosnovy avenue, 6

Russian Federation

N. V. Kondyukova

Research Institute for Complex Issues of Cardiovascular Diseases

Email: fake@neicon.ru

Junior Researcher, Laboratory of Cardiovascular Prostheses, Division of Experimental and Clinical Cardiology,

650002, Kemerovo, Sosnovy avenue, 6

Russian Federation

Yu. N. Odarenko

Research Institute for Complex Issues of Cardiovascular Diseases

Email: fake@neicon.ru

PhD, MD (Medicine), Head of the Laboratory of Cardiovascular Prostheses, Division of Experimental and Clinical Cardiology,

650002, Kemerovo, Sosnovy avenue, 6

Russian Federation

Ya. V. Kazachek

Research Institute for Complex Issues of Cardiovascular Diseases

Email: fake@neicon.ru

PhD (Medicine), Scientific Secretary,

650002, Kemerovo, Sosnovy avenue, 6

Russian Federation

A. V. Tsepokina

Research Institute for Complex Issues of Cardiovascular Diseases

Email: fake@neicon.ru

Junior Researcher, Laboratory of Genomic Medicine, Division of Experimental and Clinical Cardiology,

650002, Kemerovo, Sosnovy avenue, 6

Russian Federation

A. E. Yuzhalin

Department of Oncology, Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford

Email: fake@neicon.ru

PhD Student,

Oxford

United Kingdom

L. S. Barbarash

Research Institute for Complex Issues of Cardiovascular Diseases

Email: fake@neicon.ru

RAS Full Member, PhD, MD (Medicine), Professor, Head Researcher,

650002, Kemerovo, Sosnovy avenue, 6

Russian Federation

O. L. Barbarash

Research Institute for Complex Issues of Cardiovascular Diseases

Email: fake@neicon.ru

RAS Corresponding Member, PhD, MD (Medicine), Professor, Director,

650002, Kemerovo, Sosnovy avenue, 6

Russian Federation

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Copyright (c) 2017 Ponasenko A.V., Kutikhin A.G., Khutornaya M.V., Rutkovskaya N.V., Kondyukova N.V., Odarenko Y.N., Kazachek Y.V., Tsepokina A.V., Yuzhalin A.E., Barbarash L.S., Barbarash O.L.

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