The Health Impact of MAFLD, a Novel Disease Cluster of NAFLD, Is Amplified by the Integrated Effect of Fatty Liver Disease-Related Genetic Variants

Zhenqiu Liu; Chen Suo; Oumin Shi; Chunqing Lin; Renjia Zhao; Huangbo Yuan; Li Jin; Tiejun Zhang; Xingdong Chen

doi:10.1016/j.cgh.2020.12.033

The Health Impact of MAFLD, a Novel Disease Cluster of NAFLD, Is Amplified by the Integrated Effect of Fatty Liver Disease-Related Genetic Variants

Clin Gastroenterol Hepatol. 2022 Apr;20(4):e855-e875. doi: 10.1016/j.cgh.2020.12.033. Epub 2020 Dec 30.

Authors

Zhenqiu Liu¹, Chen Suo², Oumin Shi³, Chunqing Lin⁴, Renjia Zhao⁵, Huangbo Yuan¹, Li Jin¹, Tiejun Zhang⁵, Xingdong Chen⁶

Affiliations

¹ State Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, China; Fudan University Taizhou Institute of Health Sciences, Taizhou, China.
² Fudan University Taizhou Institute of Health Sciences, Taizhou, China; Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China; Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.
³ Health Science Center, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.
⁴ National Clinical Research Center for Cancer, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁵ Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China; Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.
⁶ State Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, China; Fudan University Taizhou Institute of Health Sciences, Taizhou, China. Electronic address: xingdongchen@fudan.edu.cn.

PMID: 33387670
DOI: 10.1016/j.cgh.2020.12.033

Abstract

Background & aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly proposed disease category that derived from non-alcoholic fatty liver disease. The impact of MAFLD on health events has not been investigated.

Methods: UK Biobank participants were diagnosed for whether MAFLD presented at baseline. Five genetic variants (PNPLA3 rs738409 C/G, TM6SF2 rs58542926 C/T, GCKR rs1260326 T/C, MBOAT7 rs641738 C/T, and HSD17B13 rs72613567 T/TA) were integrated into a genetic risk score (GRS). Cox proportional hazard model was used to examine the association of MAFLD with incident diseases.

Results: A total of 160 979 (38.0%, 95% confidence interval [CI] 37.9%, 38.2%) participants out of 423 252 were diagnosed as MAFLD. Compared with participants without MAFLD, MAFLD cases had multivariate adjusted hazard ratio (HR) for liver cancer of 1.59 (95% CI, 1.28, 1.98), cirrhosis of 2.77 (2.29, 3.36), other liver diseases of 2.09 (1.95, 2.24), cardiovascular diseases of 1.39 (1.34, 1.44), renal diseases of 1.56 (1.48, 1.65), and cancers of 1.07 (1.05, 1.10). The impact of MAFLD, especially on hepatic events, was amplified by high GRS, of which the genetic variations in PNPLA3, TM6SF2, and MBOAT7 play the principal roles. MAFLD case with normal body weight is also associated with an increased risk of hepatic outcomes, but the genetic factor seems do not influence the risk in this subpopulation.

Conclusions: MAFLD is independently associated with an increased risk of both intrahepatic and extrahepatic events. Fatty liver disease related genetic variants amplify the effect of MAFLD on disease outcomes.

Keywords: Cardiovascular Disease; Cirrhosis; Genetic Variants; Liver Cancer; MAFLD; NAFLD.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Disease Hotspot
Humans
Lipase / genetics
Membrane Proteins / genetics
Non-alcoholic Fatty Liver Disease* / epidemiology
Non-alcoholic Fatty Liver Disease* / genetics
Polymorphism, Single Nucleotide

Substances

Membrane Proteins
Lipase

Abstract

Publication types

MeSH terms

Substances

Grants and funding