Marci Laudenslager1, Mariana Lazo2, Dan Wang3, Elizabeth Selvin4, Po-Hung Chen5, James S Pankow6, Jeanne M Clark7. 1. Department of Medicine, Division of General Internal Medicine, The Johns Hopkins School of Medicine, Baltimore, MD, United States. Electronic address: mlauden1@jhmi.edu. 2. Department of Community Health and Prevention and the Urban Health Collaborative, Drexel University Dornsife School of Public Health, Philadelphia, PA, United States. Electronic address: ml3629@drexel.edu. 3. Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States. Electronic address: dwang77@jhu.edu. 4. Department of Medicine, Division of General Internal Medicine, The Johns Hopkins School of Medicine, Baltimore, MD, United States; Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States. Electronic address: eselvin@jhu.edu. 5. Department of Medicine, Division of Gastroenterology and Hepatology, The Johns Hopkins School of Medicine, Baltimore, MD, United States. Electronic address: pchen37@jhmi.edu. 6. Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, United States. Electronic address: panko001@umn.edu. 7. Department of Medicine, Division of General Internal Medicine, The Johns Hopkins School of Medicine, Baltimore, MD, United States; Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States. Electronic address: jmclark@jhmi.edu.
Abstract
BACKGROUND: Inflammation is key in the pathogenesis of Nonalcoholic Fatty Liver Disease (NAFLD) - a common progressive liver disease. The soluble receptor for advanced glycation end products (sRAGE) attenuates inflammatory signaling; low levels of sRAGE are correlated with increased inflammation. AIM: We sought to describe associations between sRAGE and NAFLD. METHODS: We conducted a cross-sectional analysis of 1088 Atherosclerosis Risk in Communities (ARIC) Study participants and used logistic regression to investigate the associations between sRAGE and NAFLD defined by elevated liver enzymes and fibrosis score. RESULTS: In this community-based sample (n = 1,088, mean age 56 years, 61% female, 78% Caucasian), persons in the lowest vs. highest quartile of sRAGE had significantly higher odds of elevated ALT (OR 2.82, 95% CI 1.18-6.76) but not elevated AST (OR 1.16, 95% CI 0.45-2.99); persons in the lowest vs. highest quartile had significantly lower odds of elevated FIB-4 index (OR 0.56, 95% CI 0.37-0.84). CONCLUSIONS: We found an inverse cross-sectional association between sRAGE and liver inflammation; this is consistent with prior studies linking low sRAGE to inflammatory states. However, we observed a direct association between sRAGE and fibrosis. Our findings suggest that sRAGE is dynamic in NAFLD and patterns may vary with different stages of disease.
BACKGROUND: Inflammation is key in the pathogenesis of Nonalcoholic Fatty Liver Disease (NAFLD) - a common progressive liver disease. The soluble receptor for advanced glycation end products (sRAGE) attenuates inflammatory signaling; low levels of sRAGE are correlated with increased inflammation. AIM: We sought to describe associations between sRAGE and NAFLD. METHODS: We conducted a cross-sectional analysis of 1088 Atherosclerosis Risk in Communities (ARIC) Study participants and used logistic regression to investigate the associations between sRAGE and NAFLD defined by elevated liver enzymes and fibrosis score. RESULTS: In this community-based sample (n = 1,088, mean age 56 years, 61% female, 78% Caucasian), persons in the lowest vs. highest quartile of sRAGE had significantly higher odds of elevated ALT (OR 2.82, 95% CI 1.18-6.76) but not elevated AST (OR 1.16, 95% CI 0.45-2.99); persons in the lowest vs. highest quartile had significantly lower odds of elevated FIB-4 index (OR 0.56, 95% CI 0.37-0.84). CONCLUSIONS: We found an inverse cross-sectional association between sRAGE and liver inflammation; this is consistent with prior studies linking low sRAGE to inflammatory states. However, we observed a direct association between sRAGE and fibrosis. Our findings suggest that sRAGE is dynamic in NAFLD and patterns may vary with different stages of disease.
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Authors: Mariana Lazo; Marc K Halushka; Lu Shen; Nisa Maruthur; Casey M Rebholz; Andreea M Rawlings; Ron C Hoogeveen; Tina E Brinkley; Christie M Ballantyne; Brad C Astor; Elizabeth Selvin Journal: Am Heart J Date: 2015-08-14 Impact factor: 4.749