ArticleEBioMedicine2021
The KLB rs17618244 gene variant is associated with fibrosing MAFLD by promoting hepatic stellate cell activation.
Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 26 citations in OpenAlex.
- β-Klotho inhibited the epithelial-mesenchymal transition of liver sinusoidal endothelial cells to alleviate schistosomiasis liver fibrosis.PLoS pathogens · 2026Article
- TheJHEP reports : innovation in hepatology · 2026Article
- Genetic modulators of metabolic dysfunction-associated steatotic liver disease (MASLD) and their epistatic interactions: from in vitro and animal models to clinical outcomes.BMC medical genomics · 2026Review
- Efimosfermin for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH): Mechanism of Action, Clinical Development and Emerging Therapeutic Potential.Drug design, development and therapy · 2026Review
- Genetic polymorphisms associated with metabolic dysfunction-associated steatotic liver disease and cardiometabolic risk susceptibility in the Chinese Han population.Human genomics · 2025Article
- Custom Gene Panel Analysis Identifies Novel Polymorphisms Associated with Clopidogrel Response in Patients Undergoing Percutaneous Coronary Intervention with Stent.International journal of molecular sciences · 2025Article
- Beta-Klotho Protein Expression in Healthy Human Tissues and Liver Biopsies From Patients With MASLD or MASH.Gastro hep advances · 2025Article
- Article
- Combined preoperative albumin bilirubin score and hepatectomy percentage for evaluate the liver regeneration after partial hepatectomy.World journal of gastroenterology · 2024Article
- Metabolic dysfunction associated fatty liver disease: The new nomenclature and its impact.World journal of gastroenterology · 2023Article
- Advances in genetic variation in metabolism-related fatty liver disease.Frontiers in genetics · 2023Review
- Biological and pharmacological functions of the FGF19- and FGF21-coreceptor beta klotho.Frontiers in endocrinology · 2023Review
- Profiling of cell-free DNA methylation and histone signatures in pediatric NAFLD: A pilot study.Hepatology communications · 2022Article
- Metabolic-associated fatty liver disease from childhood to adulthood: State of art and future directions.World journal of hepatology · 2022Review
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe rs17618244 G>A β-Klotho (KLB) variant has been associated with increased risk of ballooning and inflammation in pediatric patients with metabolic associated fatty liver disease (MAFLD), by reducing KLB expression. In hepatocytes, KLB downregulation induced fat accumulation and the expression of inflammatory and lipotoxic genes. We aimed to examine firstly the impact of the KLB rs17618244 variation on liver damage in adult patients with MAFLD and secondly its effect on hepatic stellate cells (HSCs) activation.
methodsThe impact of the KLB rs17618244 variant on histological liver damage was surveyed in a retrospective cohort of 1111 adult patients with MAFLD. Subgroup analysis was performed according to the presence of obesity (BMI>35; n = 708). Immortalized HSCs (LX-2) were transfected with the KLB wild type (LX-2_KLBwt), or with the mutant one carrying the rs17618244 (LX-2_KLBmut).
findingsAt ordinal regression analysis the KLB rs17618244 variant was associated with hepatic fibrosis (OR 1.23, 95% C.I.1.004-1.51; p = 0.04), but not with steatosis, inflammation and ballooning. By stratifying patients according to the presence of obesity, the KLB A allele was further associated with lobular inflammation (OR 1.32, 95% C.I.1.02-1.72; p = 0.03) and cirrhosis (OR 2.51, 95% C.I.1.23-5.05; p = 0.01) Moreover, hepatic KLB expression correlated with that of fibrogenic genes. LX-2_KLBmut cells showed reduced KLB protein levels paralleled by an induction of pro-fibrogenic genes and enhanced proliferative rate.
interpretationThe KLB rs17618244 variant is associated with hepatic fibrosis, inflammation and cirrhosis mainly in obese patients with MAFLD and HSCs which carry this mutation are highly proliferative and acquire a myofibroblast-like phenotype.
fundingRicerca Finalizzata Ministero della Salute GR-2019-12,370,172 (NP), Ricerca Corrente Fondazione IRCCS Cà Granda (PD and ALF), Ricerca Finalizzata Ministero della Salute RF-2013-02,358,319 (ALF), and Ricerca Corrente and 5 × 1000 Ministero della Salute (AA).
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