Inflammasome genes polymorphisms may influence the development of hepatitis C in the Amazonas, Brazil
Autor: | Nadja Pinto Garcia, Juliana dos Santos Affonso, Aya Sadahiro, Jéssica Albuquerque da Silva, Adriana Malheiro, Hanna Lara Silva Negreiros Dray, Rajendranath Ramasawmy, Mauricio Morishi Ogusku, Flamir da Silva Victoria, Diana Mota Toro, Grenda Leite Pereira, Pedro Vieira da Silva Neto, Allyson Guimarães Costa, Keyla Santos de Sousa, Marilú Victória Barbieri, Eduardo Antônio Donadi, Andréa Monteiro Tarragô, Priscila Santos Sarmento |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
RNA viruses
Male Linkage disequilibrium Heredity Gastroenterology and hepatology Inflammasomes Physiology Interleukin-1beta Hepacivirus medicine.disease_cause Biochemistry Homozygosity Hepatitis Cathepsin B Gene Frequency Fibrosis Polymorphism (computer science) Immune Physiology Genotype Medicine Pathology and laboratory medicine Innate Immune System Multidisciplinary Immune System Proteins Heterozygosity Hepatitis C virus Interleukin-18 Hepatitis C Medical microbiology Middle Aged Neoplasm Proteins DNA-Binding Proteins Infectious hepatitis Viruses Infectious diseases Cytokines Interleukin 18 Female Pathogens Brazil Research Article Medical conditions Adult Science Immunology Viral diseases Microbiology Polymorphism Single Nucleotide Young Adult NLR Family Pyrin Domain-Containing 3 Protein Genetics Humans Genetic Predisposition to Disease Allele Alleles Liver diseases Aged Medicine and health sciences Flaviviruses business.industry GENÓTIPOS Organisms Viral pathogens Biology and Life Sciences Proteins Molecular Development medicine.disease Hepatitis viruses Microbial pathogens CARD Signaling Adaptor Proteins Genetic Loci Immune System business Developmental Biology |
Zdroj: | PLoS ONE PLoS ONE, Vol 16, Iss 6, p e0253470 (2021) Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
ISSN: | 1932-6203 |
Popis: | Hepatitis C is considered a major public health problem caused by the hepatitis C virus (HCV). Viral infections are known to induce production of IL1β through the signaling pathway of inflammasomes. Emerging evidences suggest that Inflammasome genes may influence the immune response against HCV as the host genetic background may contribute to the balance between acute and chronic inflammation. We investigated in 151 patients with chronic hepatitis C and 206 healthy blood donors’ individuals (HD). Polymorphisms in the IL1B and IL18 genes were genotyped by PCR-RFLP, while NLRP3, CARD8, CTSB and AIM2 by RT- PCR. Serum assay of IL-1β cytokine was performed by ELISA. 84 patients presented mild fibrosis (NLRP3-rs10754558 C/C genotype correlated with higher IL-1β levels compared to the G/G genotype. Similar pattern was observed in patients with hepatitis C, mean circulating IL-1β levels were 21,96 ± 4.5 and 10,62 ± 3.3pg/mL among the C/C and G/G genotypes, respectively. This pattern holds even after stratification of the patients into mild fibrosis and advanced fibrosis, demonstrating that the NLRP3-rs10754558 or another polymorphism in linkage disequilibrium with it possibly has an influence on the processing of pro-IL-1β. Notably, higher levels of IL-1β (Mann–Whitney test, pCARD8-rs2009373 and IL1B-rs16944 are less prone to hepatitis C development (padj = 0.039). Similarly, herozygote carriers for CTSB-rs1692816 and AIM2-rs1103577 (padj = 0.008) or for IL18-rs187238 and NLRP3-rs10754558 (padj = 0.005), have less chances to the development of hepatitis C. However, between subgroups of CARD8-rs2009373 and heterozygous for IL18-rs187238 (padj = 0.028), have mild form of fibrosis. |
Databáze: | OpenAIRE |
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