Journal of Clinical and Translational Hepatology

Journal of Clinical and Translational Hepatology

Thursday, 05 / 13 / 2021

Articles

Abstract

ORIGINAL ARTICLE

Associations of Hydroxysteroid 17-beta Dehydrogenase 13 Variants with Liver Histology in Chinese Patients with Metabolic-associated Fatty Liver Disease

Wen-Yue Liu1,#, Mohammed Eslam2,#, Kenneth I. Zheng3, Hong-Lei Ma3, Rafael S. Rios3Min-Zhi Lv4, Gang Li, Liang-Jie Tang, Pei-Wu Zhu, Xiao-Dong Wang3,6 , Christopher D. Byrne, Giovanni Targher8, Jacob Georgeg2,* and Ming-Hua Zhengn3,6,9,*

1  Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
2  Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, Sydney, Australia
3  NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
4  Department of Biostatistics, Zhongshan Hospital, Fudan University, Shanghai, China
5  Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
6  Institute of Hepatology, Wenzhou Medical University, Wenzhou, Zhejiang, China
7  Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK
8  Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
9  Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, Zhejiang, China
*Correspondence to: Ming-Hua Zheng, NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University; No. 2 Fuxue Lane, Wenzhou Zhejiang 325000, China. ORCID: http://orcid.org/0000-0003-4984-2631. Tel: +86-577-55579611, Fax: +86-577-55578522, E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. ; Jacob George, Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, Sydney 2145, Australia. Tel: +61-2-88907705, Fax: +61-2-96357582, E-mail:  This email address is being protected from spambots. You need JavaScript enabled to view it.

Journal of Clinical and Translational Hepatology 2021;9(2):194-202 DOI: 10.14218/JCTH.2020.00151
Received: November 12, 2020 Accepted: February 4, 2021 Published online: March 11, 2021

Abstract

Background and Aims: In Europeans, variants in the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) gene impact liver histology in metabolic-associated fatty liver disease (MAFLD). The impact of these variants in ethnic Chinese is unknown. The aim of this study was to investigate the potential associations in Chinese patients.

Methods: In total, 427 Han Chinese with biopsy-confirmed MAFLD were enrolled. Two single nucleotide polymorphisms in HSD17B13 were genotyped: rs72613567 and rs6531975. Logistic regression was used to test the association between the single nucleotide polymorphisms and liver histology.

Results: In our cohort, the minor allele TA of the rs72613567 variant was related to an increased risk of fibrosis [odds ratio (OR): 2.93 (1.20–7.17), p=0.019 for the additive model; OR: 3.32 (1.39–7.91), p=0.007 for the recessive model], representing an inverse association as compared to the results from European cohorts. In contrast, we observed a protective effect on fibrosis for the minor A allele carriers of the HSD17B13 rs6531975 variant [OR: 0.48 (0.24–0.98), p=0.043 for the additive model; OR: 0.62 (0.40–0.94), p=0.025 for the dominant model]. HSD17B13 variants were only associated with fibrosis but no other histological features. Furthermore, HSD17B13 rs6531975 modulated the effect of PNPLA3 rs738409 on hepatic steatosis.

Conclusions: HSD17B13 rs72613567 is a risk variant for fibrosis in a Han Chinese MAFLD population but with a different direction for allelic association to that seen in Europeans. These data exemplify the need for studying diverse populations in genetic studies in order to fine map genome-wide association studies signals.

Keywords

Metabolic-associated fatty liver disease (MAFLD), Nonalcoholic fatty liver disease (NAFLD), Hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13), Single nucleotide polymorphism (SNP)

Journal of Clinical and Translational Hepatology 2021 vol. 9, 194-202  [ Html  ] [ PDF Full-text ]

© 2021 Authors. This is an Open Access article distributed under the terms of the  Creative Commons Attribution-Noncommercial 4.0 License(CC BY-NC 4.0), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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