Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms
Year: 2016
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a complex, multifactorial disease affected by diet, lifestyle and genetics. Proinflammatory cytokines like IL-1β and IL-6 have been shown to be elevated in non-alcoholic steatohepatitis (NASH). AIM: To investigate the relationship between IL1B and IL6 gene polymorphisms and histological features of NAFLD in the NASH CRN cohort. METHODS: A total of 604 adult (≥18 years) non-Hispanic Caucasians with biopsy-proven NAFLD were genotyped for the following SNPs: IL1B, rs16944, rs1143634; IL6, rs1800795, rs10499563. Logistic regression was used to examine the relationship between genotype and a definitive diagnosis and advanced histological features of NASH after controlling for the following variables selected a priori: age, sex, diabetes, obesity and HOMA-IR level. RESULTS: The IL6 rs10499563 C allele was independently associated with the presence of definitive NASH, and increased ballooning and Mallory bodies. The IL1B rs1143634 TT genotype was associated with advanced fibrosis and increased Mallory bodies. The IL6 rs1800795 C allele was associated with not only increased risk for severe steatosis, >66% but also decreased risk for advanced fibrosis and lobular inflammation and Mallory body formation. CONCLUSIONS: These results suggest that common variants in the IL6 and IL1B genes may increase susceptibility for NASH and confer a higher risk of hepatic parenchymal damage including increased ballooning, increased Mallory bodies, and bridging fibrosis or cirrhosis. In contrast, the IL6 rs1800795 C allele may confer a higher risk for steatosis, but less parenchymal damage. Our findings support the development of therapeutics aimed at IL-1β and IL-6 suppression.
DOI: 10.1111/apt.13824
Authors: J. E. Nelson, P. Handa, B. Aouizerat, L. Wilson, L. A. Vemulakonda, M. M. Yeh, K. V. Kowdley
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network, Indiana Clinical and Translational Sciences Institute, San Diego Clinical and Translational Research Institute, Institute of Translational Health Sciences, Duke CTSA, Northwestern University Clinical and Translational Science Institute (NUCATS), Center for Clinical and Translational Research, Multidisciplinary Clinical and Translational Science (MCTS) Program (UL1), Clinical and Translational Science Institute, Atlanta Clinical and Translational Science Institute (ACTSI) Renewal, Patient Oriented Research & Mentoring in liver diseases, Washington University Institute of Clinical and Translational Sciences, Institute for Clinical and Translational Research, The Role of Iron in the Pathogenesis of NAFLD, Indiana Clinical and Translational Science Institute (UL1), Clinical and Translational Science Award, Clinical and Translational Science Collaborative of Cleveland, Cincinnati Center for Clinical and Translational Sciences and Training, Mount Sinai Institutes for Clinical and Translational Sciences, Short-Term Institutional Research Training Grant, Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN), Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN), Digestive Health Center (DHC): Bench to Bedside Research in Pediatric Digestive Disease, Clinical Research Network in Nonalcoholic Steatohepatitis, Collaborative Clinical Research in Nonalcoholic Steatohepatitis, Institute of Translational Health Sciences, Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Clinical Center-Cleveland site, Clinical Research on Nonalcoholic Fatty Liver Disease, The Saint Louis University Component of the NASH Clinical Research Network, Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)
OpenAlex ID: W2530710771