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

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...

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Autores principales: A. V. Ponasenko, A. G. Kutikhin, M. V. Khutornaya, N. V. Rutkovskaya, N. V. Kondyukova, Yu. N. Odarenko, Ya. V. Kazachek, A. V. Tsepokina, A. E. Yuzhalin, L. S. Barbarash, O. L. Barbarash
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Publicado: Sankt-Peterburg : NIIÈM imeni Pastera 2017
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spelling oai:doaj.org-article:bc59da92b2424000a4c48fe714e0888e2021-11-22T07:09:48ZPOLYMORPHISMS WITHIN INNATE IMMUNE RESPONSE, CALCIUM METABOLISM AND LIPID METABOLISM ARE PREDICTORS OF INFECTIVE ENDOCARDITIS2220-76192313-739810.15789/2220-7619-2017-2-130-140https://doaj.org/article/bc59da92b2424000a4c48fe714e0888e2017-06-01T00:00:00Zhttps://www.iimmun.ru/iimm/article/view/513https://doaj.org/toc/2220-7619https://doaj.org/toc/2313-7398Infective 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.A. V. PonasenkoA. G. KutikhinM. V. KhutornayaN. V. RutkovskayaN. V. KondyukovaYu. N. OdarenkoYa. V. KazachekA. V. TsepokinaA. E. YuzhalinL. S. BarbarashO. L. BarbarashSankt-Peterburg : NIIÈM imeni Pasteraarticleinfective endocarditissingle nucleotide polymorphismspredictive markersil-1βil-12c-reactive proteinInfectious and parasitic diseasesRC109-216RUInfekciâ i Immunitet, Vol 7, Iss 2, Pp 130-140 (2017)
institution DOAJ
collection DOAJ
language RU
topic infective endocarditis
single nucleotide polymorphisms
predictive markers
il-1β
il-12
c-reactive protein
Infectious and parasitic diseases
RC109-216
spellingShingle infective endocarditis
single nucleotide polymorphisms
predictive markers
il-1β
il-12
c-reactive protein
Infectious and parasitic diseases
RC109-216
A. V. Ponasenko
A. G. Kutikhin
M. V. Khutornaya
N. V. Rutkovskaya
N. V. Kondyukova
Yu. N. Odarenko
Ya. V. Kazachek
A. V. Tsepokina
A. E. Yuzhalin
L. S. Barbarash
O. L. Barbarash
POLYMORPHISMS WITHIN INNATE IMMUNE RESPONSE, CALCIUM METABOLISM AND LIPID METABOLISM ARE PREDICTORS OF INFECTIVE ENDOCARDITIS
description 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.
format article
author A. V. Ponasenko
A. G. Kutikhin
M. V. Khutornaya
N. V. Rutkovskaya
N. V. Kondyukova
Yu. N. Odarenko
Ya. V. Kazachek
A. V. Tsepokina
A. E. Yuzhalin
L. S. Barbarash
O. L. Barbarash
author_facet A. V. Ponasenko
A. G. Kutikhin
M. V. Khutornaya
N. V. Rutkovskaya
N. V. Kondyukova
Yu. N. Odarenko
Ya. V. Kazachek
A. V. Tsepokina
A. E. Yuzhalin
L. S. Barbarash
O. L. Barbarash
author_sort A. V. Ponasenko
title POLYMORPHISMS WITHIN INNATE IMMUNE RESPONSE, CALCIUM METABOLISM AND LIPID METABOLISM ARE PREDICTORS OF INFECTIVE ENDOCARDITIS
title_short POLYMORPHISMS WITHIN INNATE IMMUNE RESPONSE, CALCIUM METABOLISM AND LIPID METABOLISM ARE PREDICTORS OF INFECTIVE ENDOCARDITIS
title_full POLYMORPHISMS WITHIN INNATE IMMUNE RESPONSE, CALCIUM METABOLISM AND LIPID METABOLISM ARE PREDICTORS OF INFECTIVE ENDOCARDITIS
title_fullStr POLYMORPHISMS WITHIN INNATE IMMUNE RESPONSE, CALCIUM METABOLISM AND LIPID METABOLISM ARE PREDICTORS OF INFECTIVE ENDOCARDITIS
title_full_unstemmed POLYMORPHISMS WITHIN INNATE IMMUNE RESPONSE, CALCIUM METABOLISM AND LIPID METABOLISM ARE PREDICTORS OF INFECTIVE ENDOCARDITIS
title_sort polymorphisms within innate immune response, calcium metabolism and lipid metabolism are predictors of infective endocarditis
publisher Sankt-Peterburg : NIIÈM imeni Pastera
publishDate 2017
url https://doaj.org/article/bc59da92b2424000a4c48fe714e0888e
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