Protective association of Klotho rs495392 gene polymorphism against hepatic steatosis in non-alcoholic fatty liver disease patients.
Klotho
Non-alcoholic fatty liver disease
rs495392
vitamin D
Journal
Clinical and molecular hepatology
ISSN: 2287-285X
Titre abrégé: Clin Mol Hepatol
Pays: Korea (South)
ID NLM: 101586730
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
20
09
2021
accepted:
27
11
2021
pubmed:
30
11
2021
medline:
20
4
2022
entrez:
29
11
2021
Statut:
ppublish
Résumé
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. 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. 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. The KL rs495392 polymorphism has a protective effect against hepatic steatosis in patients with NAFLD.
Sections du résumé
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.
CONCLUSION
The KL rs495392 polymorphism has a protective effect against hepatic steatosis in patients with NAFLD.
Identifiants
pubmed: 34839623
pii: cmh.2021.0301
doi: 10.3350/cmh.2021.0301
pmc: PMC9013609
doi:
Substances chimiques
Membrane Proteins
0
Vitamin D
1406-16-2
Lipase
EC 3.1.1.3
KL protein, human
EC 3.2.1.31
Klotho Proteins
EC 3.2.1.31
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
183-195Références
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