FNDC5 polymorphism influences the association between sarcopenia and liver fibrosis in adults with biopsy-proven nonalcoholic fatty liver disease
FNDC5 polymorphism influences the association between sarcopenia and liver fibrosis in adults with biopsy-proven nonalcoholic fatty liver disease
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.
KEY-WORDS:, Nonalcoholic fatty liver disease, SNP, Sarcopenia, Skeletal muscle
813-824
Gao, Feng
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Zheng, Kenneth I.
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Zhu, Pei-Wu
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Li, Yang-Yang
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Ma, Hong-Lei
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Li, Gang
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Tang, Liang-Jie
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Rios, Rafael S.
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Liu, Wen-Yue
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Pan, Xiao-Yan
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Targher, Giovanni
043e0811-b389-4922-974e-22e650212c5f
Byrne, Christopher
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Chen, Yong-Ping
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Zheng, Ming-Hua
6df10db4-1777-491c-ac7a-ec082c911188
28 September 2021
Gao, Feng
b70fc7ee-1c00-4b32-aa1a-272e603a3add
Zheng, Kenneth I.
1846629d-e432-4b2d-9e4e-5462cd13b8d6
Zhu, Pei-Wu
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Li, Yang-Yang
48372b97-1d10-4826-8658-73639adfb416
Ma, Hong-Lei
6fded360-a4ae-48d1-aa42-88e1f1cbc9f7
Li, Gang
3321642a-de7d-4dc6-bcfc-c7564acad0c9
Tang, Liang-Jie
18e6dc85-09a0-458c-b188-2a1c36cf854e
Rios, Rafael S.
22498624-83b7-46bd-8bb5-f8e102e5ad01
Liu, Wen-Yue
0fbd711d-011e-4c00-b9a0-955bffb86a52
Pan, Xiao-Yan
bcf0d9fb-89a8-4c6b-8075-f2be090e3bdd
Targher, Giovanni
043e0811-b389-4922-974e-22e650212c5f
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Chen, Yong-Ping
3ff6a2c0-378c-42a0-9504-dd5b95c49052
Zheng, Ming-Hua
6df10db4-1777-491c-ac7a-ec082c911188
Gao, Feng, Zheng, Kenneth I., Zhu, Pei-Wu, Li, Yang-Yang, Ma, Hong-Lei, Li, Gang, Tang, Liang-Jie, Rios, Rafael S., Liu, Wen-Yue, Pan, Xiao-Yan, Targher, Giovanni, Byrne, Christopher, Chen, Yong-Ping and Zheng, Ming-Hua
(2021)
FNDC5 polymorphism influences the association between sarcopenia and liver fibrosis in adults with biopsy-proven nonalcoholic fatty liver disease.
British Journal of Nutrition, 126 (6), .
(doi:10.1017/S0007114520004559).
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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Accepted/In Press date: 9 November 2020
e-pub ahead of print date: 17 November 2020
Published date: 28 September 2021
Additional Information:
Funding Information:
This work was supported by grants from the National Natural Science Foundation of China (81500665, 82070588), High Level Creative Talents from Department of Public Health in Zhejiang Province (S2032102600032) and Project of New Century 551 Talent Nurturing in Wenzhou. GT is supported in part by grants from the School of Medicine, University of Verona, Verona, Italy. CDB is supported in part by the Southampton NIHR Biomedical Research Centre (IS-BRC-20004), UK.
Publisher Copyright:
© 2021 Cambridge University Press. All rights reserved.
Keywords:
KEY-WORDS:, Nonalcoholic fatty liver disease, SNP, Sarcopenia, Skeletal muscle
Identifiers
Local EPrints ID: 445132
URI: http://eprints.soton.ac.uk/id/eprint/445132
ISSN: 0007-1145
PURE UUID: af1715aa-e70b-4b4e-9c15-9ac4822340c1
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Date deposited: 20 Nov 2020 17:32
Last modified: 17 Mar 2024 06:04
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Contributors
Author:
Feng Gao
Author:
Kenneth I. Zheng
Author:
Pei-Wu Zhu
Author:
Yang-Yang Li
Author:
Hong-Lei Ma
Author:
Gang Li
Author:
Liang-Jie Tang
Author:
Rafael S. Rios
Author:
Wen-Yue Liu
Author:
Xiao-Yan Pan
Author:
Giovanni Targher
Author:
Yong-Ping Chen
Author:
Ming-Hua Zheng
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