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FNDC5 polymorphism influences the association between sarcopenia and liver fibrosis in adults with biopsy-proven non-alcoholic fatty liver disease

Published online by Cambridge University Press:  17 November 2020

Feng Gao
Affiliation:
Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China
Kenneth I. Zheng
Affiliation:
Department of Hepatology, NAFLD Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China
Pei-Wu Zhu
Affiliation:
Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China
Yang-Yang Li
Affiliation:
Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China
Hong-Lei Ma
Affiliation:
Department of Hepatology, NAFLD Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China
Gang Li
Affiliation:
Department of Hepatology, NAFLD Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China
Liang-Jie Tang
Affiliation:
Department of Hepatology, NAFLD Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China
Rafael S. Rios
Affiliation:
Department of Hepatology, NAFLD Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China
Wen-Yue Liu
Affiliation:
Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China
Xiao-Yan Pan
Affiliation:
Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China
Giovanni Targher
Affiliation:
Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37100 Verona, Italy
Christopher D. Byrne
Affiliation:
Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton SO16 6YD, UK
Yong-Ping Chen
Affiliation:
Department of Hepatology, NAFLD Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China Institute of Hepatology, Wenzhou Medical University, Wenzhou 325000, People’s Republic of China Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou 325000, People’s Republic of China
Ming-Hua Zheng
Affiliation:
Department of Hepatology, NAFLD Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China Institute of Hepatology, Wenzhou Medical University, Wenzhou 325000, People’s Republic of China Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou 325000, People’s Republic of China
Corresponding
E-mail address:

Abstract

The FNDC5 gene encodes the fibronectin type III domain-containing protein 5 that is a membrane protein mainly expressed in skeletal muscle, and the FNDC5 rs3480 polymorphism may be associated with liver disease severity in non-alcoholic fatty liver disease (NAFLD). We investigated the influence of the FNDC5 rs3480 polymorphism on the relationship between sarcopenia and the histological severity of NAFLD. A total of 370 adult individuals with biopsy-proven NAFLD were studied. The association between the key exposure sarcopenia and the outcome liver histological severity was investigated by binary logistic regression. Stratified analyses were undertaken to examine the impact of FNDC5 rs3480 polymorphism on the association between sarcopenia and the severity of NAFLD histology. Patients with sarcopenia had more severe histological grades of steatosis and a higher prevalence of significant fibrosis and definite non-alcoholic steatohepatitis than those without sarcopenia. There was a significant association between sarcopenia and significant fibrosis (adjusted OR 2·79, 95 % CI 1·31, 5·95, P = 0·008), independent of established risk factors and potential confounders. Among patients with sarcopenia, significant fibrosis occurred more frequently in the rs3480 AA genotype carriers than in those carrying the FNDC5 rs3480 G genotype (43·8 v. 17·2 %, P = 0·031). In the association between sarcopenia and liver fibrosis, there was a significant interaction between the FNDC5 genotype and sarcopenia status (P value for interaction = 0·006). Sarcopenia is independently associated with significant liver fibrosis, and the FNDC5 rs3480 G variant influences the association between sarcopenia and liver fibrosis in patients with biopsy-proven NAFLD.

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Full Papers
Copyright
© The Author(s), 2020. Published by Cambridge University Press on behalf of The Nutrition Society

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FNDC5 polymorphism influences the association between sarcopenia and liver fibrosis in adults with biopsy-proven non-alcoholic fatty liver disease
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