دورية أكاديمية
Polymorphisms in the interleukin (IL)-1 gene cluster influence systemic inflammation in patients at risk for acute-on-chronic liver failure.
| العنوان: | Polymorphisms in the interleukin (IL)-1 gene cluster influence systemic inflammation in patients at risk for acute-on-chronic liver failure. |
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| المؤلفون: | Alcaraz Quiles, J, Titos, E, Casulleras, M, Pavesi, M, López Vicario, C, Rius, B, Lopategi, A, de Gottardi, A, Graziadei, I, Gronbaek, H, Ginès, P, Arroyo, V, Clària, J., BERNARDI, MAURO |
| المساهمون: | Alcaraz-Quiles, J, Titos, E, Casulleras, M, Pavesi, M, López-Vicario, C, Rius, B, Lopategi, A, de Gottardi, A, Graziadei, I, Gronbaek, H, Ginès, P, Bernardi, M, Arroyo, V, Clària, J. |
| سنة النشر: | 2017 |
| المجموعة: | IRIS Università degli Studi di Bologna (CRIS - Current Research Information System) |
| مصطلحات موضوعية: | Interleukin, polymorphism, cirrhosi, acute-on-chronic liver failure, systemic inflammation |
| الوصف: | Acute-on-chronic liver failure (ACLF) in cirrhosis is an increasingly recognized syndrome characterized by acute decompensation, organ failure(s) and high short-term mortality. Recent findings suggest that an over-exuberant systemic inflammation plays a primary role in ACLF progression. In this study, we examined whether genetic factors shape systemic immune responses in patients with decompensated cirrhosis. Six single nucleotide polymorphisms (SNPs) in inflammation-related genes (IL-1β: rs1143623, IL-1ra: rs4251961, IL-10: rs1800871, SOCS3: rs4969170, NOD2: rs3135500 and CMKLR1: rs1878022) were genotyped in 279 cirrhotic patients with (n=178) and without (n=101) ACLF from the CANONIC study of the CLIF consortium. Among these SNPs, we identified two polymorphisms belonging to the IL-1 gene cluster (IL-1β and IL-1ra) in strong association with ACLF. Both SNPs were protective against ACLF; IL-1β (OR: 0.34, 95% CI 0.13-0.89, p<0.05) and IL-1ra (OR: 0.58, 95% CI 0.35-0.95, p<0.05) under the recessive and overdominant inheritance models, respectively. These protective SNPs translated into reduced circulating levels of IL-1β, IL-1α, IL-6, G-CSF, GM-CSF and C-reactive protein at enrolment as well as after 7-14 days of admission. These findings were confirmed in vitro in leukocytes incubated with plasma from patients with decompensated cirrhosis carrying the protective SNP genotypes. Notably, a higher frequency of the protective genotypes was seen in patients without (80%) than in those with (20%) ACLF. Consistently, patients carrying the combined protective genotypes showed a lower 28-day mortality rate. CONCLUSION: These data identify two common functional polymorphisms in the IL-1 gene cluster which are associated with the inflammatory process related to the development of ACLF. This article is protected by copyright. All rights reserved. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | STAMPA |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/27775822; info:eu-repo/semantics/altIdentifier/wos/WOS:000397298600019; volume:65; firstpage:202; lastpage:216; numberofpages:15; journal:HEPATOLOGY; http://hdl.handle.net/11585/588482Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85006147272 |
| DOI: | 10.1002/hep.28896 |
| الإتاحة: | https://doi.org/10.1002/hep.28896Test http://hdl.handle.net/11585/588482Test |
| رقم الانضمام: | edsbas.39D01DC9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/hep.28896 |
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