Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis

Abstract

Infective endocarditis (IE) is a septic inflammation of the endocardium. 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. Having recruited 123 patients with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in the abovementioned pathways, with the further 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 were associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene was 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. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE.

Human Genetic Susceptibility to Native Valve Staphylococcus aureus Endocarditis in Patients With S. aureus Bacteremia: Genome-Wide Association Study

“…Analyzes were made on small cohorts of IE patients compared to healthy blood donors and targeted a priori candidates such as genes involved in inflammation. Polymorphisms in TLR6, IL1B, IL12B, CRP and CALCR genes but not IL6 and TNF were associated with a decreased risk of IE ( Golovkin et al, 2015 ; Ponasenko et al, 2017 ) while SNPs in IL1B, IL6,TLR2 and TNF genes were associated with IE ( Bustamante et al, 2011 ; Giannitsioti et al, 2014 ; Weinstock et al, 2014 ) as compared to healthy donors. None of these SNPs were identified in the present study, perhaps because our study focused on S. aureus only and our comparator group was S. aureus bacteremia patients.…”

Polymorphism of protein genes associated with endothelial function in patients with infective endocarditis

“…Экспрессируется в основном в фибробластах кожи, нейронной ткани и первичных эндотелиальных клетках, и, как прогнозируется, белок опосредует лизосомальное поглощение катионных аминокислот. Авторы не нашли никакой связи с вариабельностью генов врождённого иммунного и воспалительного ответа, ранее описанных в литературе [22][23][24][25], или с генами эндотелиальной функции [26]. Однако сами исследователи сообщают, что основным ограничением проведенного ими исследования является отсутствие статистической значимости результатов, полученных в GWAS, за счет малых размеров выборки, анализа только S.aureusассоци ированного ИЭ и скудной информации о функции белка SLC7A14, что затрудняет интерпретацию его роли в патофизиологическом механизме, связывающем экспрессию этого гена с появлением ИЭ.…”

Predicting the Structures of Glycans, Glycoproteins, and Their Complexes

“…Thus, despite the biological importance of calcium–carbohydrate interactions, additional experimental and theoretical studies will be required to establish the accuracy of MD simulations of these systems. Although significant for many diseases, from cystic fibrosis , to endocarditis, the complex calcium-mediated aggregation of polysaccharide biofilms represents a particularly challenging class of structure to model. , …”