Clin Mol Hepatol.
2022 Apr;28(2):183-195. 10.3350/cmh.2021.0301.
Protective association of Klotho rs495392 gene polymorphism against hepatic steatosis in non-alcoholic fatty liver disease patients
- Liu WY1
- Zhang X2
- Li G3
- Tang LJ3
- Zhu PW4
- Rios RS3
- Zheng KI3
- Ma HL3
- Wang XD5
- Pan Q6
- de Knegt RJ6
- Valenti L7,8
- Ghanbari M
2 - Zheng MH3,5,9
- Affiliations
-
- 1Department of Endocrinology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- 2Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
- 3NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- 4Department of Laboratory Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- 5Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
- 6Department of Gastroenterology and Hepatology, Erasmus MC, Erasmus University Medical Center, Rotterdam, the Netherlands
- 7Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milano, Milan, Italy
- 8Department of Pathophysiology and Transplantation, University of Milan, Milano, Italy
- 9Institute of Hepatology, Wenzhou Medical University, Wenzhou, China
- KMID: 2528248
- DOI: http://doi.org/10.3350/cmh.2021.0301
Abstract
- Background/Aims
Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic dysfunction. Among the multiple factors, genetic variation acts as important modifiers. Klotho, an enzyme encoded by the klotho (KL) gene in human, has been implicated in the pathogenesis of metabolic dysfunctions. However, the impact of variants in KL on NAFLD risk remains poorly understood. The aim of this study was to investigate the impact of KL rs495392 C>A polymorphism on the histological severity of NAFLD.
Methods
We evaluated the impact of the KL rs495392 polymorphism on liver histology in 531 Chinese with NAFLD and replicated that in the population-based Rotterdam Study cohort. The interactions between the rs495392, vitamin D, and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 polymorphism were also analyzed.
Results
Carriage of the rs495392 A allele had a protective effect on steatosis severity (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.42–0.89; P=0.010) in Chinese patients. After adjustment for potential confounders, the A allele remained significant with a protective effect (OR, 0.66; 95% CI, 0.45–0.98; P=0.040). The effect on hepatic steatosis was confirmed in the Rotterdam Study cohort. Additional analysis showed the association between serum vitamin D levels and NAFLD specifically in rs495392 A allele carriers, but not in non-carriers. Moreover, we found that the rs495392 A allele attenuated the detrimental impact of PNPLA3 rs738409 G allele on the risk of severe hepatic steatosis.
Conclusions
The KL rs495392 polymorphism has a protective effect against hepatic steatosis in patients with NAFLD.
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