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Cytokine gene functional polymorphisms and phenotypic expression as predictors of evolution from latent to clinical rheumatic heart disease.
- Source :
-
Cytokine [Cytokine] 2021 Feb; Vol. 138, pp. 155370. Date of Electronic Publication: 2020 Dec 19. - Publication Year :
- 2021
-
Abstract
- Introduction: Inflammation associated with rheumatic heart disease (RHD) is influenced by gene polymorphisms and inflammatory cytokines. There are currently no immunologic and genetic markers to discriminate latent versus clinical patients, critical to predict disease evolution. Employing machine-learning, we searched for predictors that could discriminate latent versus clinical RHD, and eventually identify latent patients that may progress to clinical disease.<br />Methods: A total of 212 individuals were included, 77 with latent, 100 with clinical RHD, and 35 healthy controls. Circulating levels of 27 soluble factors were evaluated using Bio-Plex ProTM® Human Cytokine Standard 27-plex assay. Gene polymorphism analyses were performed using RT-PCR for the following genes: IL2, IL4, IL6, IL10, IL17A, TNF and IL23.<br />Results: Serum levels of all cytokines were higher in clinical as compared to latent RHD patients, and in those groups than in controls. IL-4, IL-8, IL-1RA, IL-9, CCL5 and PDGF emerged in the final multivariate model as predictive factors for clinical, compared with latent RHD. IL-4, IL-8 and IL1RA had the greater power to predict clinical RHD. In univariate analysis, polymorphisms in IL2 and IL4 were associated with clinical RHD and in the logistic analysis, IL6 (GG + CG), IL10 (CT + TT), IL2 (CA + AA) and IL4 (CC) genotypes were associated with RHD.<br />Conclusion: Despite higher levels of all cytokines in clinical RHD patients, IL-4, IL-8 and IL-1RA were the best predictors of clinical disease. An association of polymorphisms in IL2, IL4, IL6 and IL10 genes and clinical RHD was observed. Gene polymorphism and phenotypic expression of IL-4 accurately discriminate latent versus clinical RHD, potentially instructing clinical management.<br /> (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Subjects :
- Adolescent
Adult
Alleles
Child
Female
Gene Expression Regulation
Gene Frequency
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Humans
Inflammation
Machine Learning
Male
Middle Aged
Phenotype
Prognosis
Cytokines genetics
Cytokines metabolism
Disease Progression
Polymorphism, Single Nucleotide
Rheumatic Heart Disease genetics
Rheumatic Heart Disease physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0023
- Volume :
- 138
- Database :
- MEDLINE
- Journal :
- Cytokine
- Publication Type :
- Academic Journal
- Accession number :
- 33341346
- Full Text :
- https://doi.org/10.1016/j.cyto.2020.155370