The HSD17B13 rs72613567 variant is associated with lower levels of albuminuria in patients with biopsy-proven nonalcoholic fatty liver disease

Sun, Dan‐Qin; Wang, Ting-Yao; Zheng, Kenneth I.; Zhang, Hao-Yang; Wang, Xiaodong; Targher, Giovanni; Byrne, Christopher D.; Chen, Yongping; Wang, Yuan; Jin, Yan; Zheng, Ming‐Hua

doi:10.1016/j.numecd.2021.02.018

Cited by 14 publications

(12 citation statements)

References 42 publications

(52 reference statements)

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“…However, in another study involving 215 Chinese adults with biopsy-proven NAFLD, the A/-or A/A HSD17B13 genotypes were associated with a lower risk of abnormal albuminuria, but not with altered levels of eGFR or urinary neutrophil gelatinase-associated lipocalin 82 .…”

Section: Genetic Predispositionmentioning

confidence: 90%

Association of metabolic dysfunction-associated fatty liver disease with kidney disease

Wang

et al. 2022

Nat Rev Nephrol

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107

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Nature Reviews publishes timely, authoritative articles that are of broad interest and exceptional quality. Thank you for taking the time to help us to ensure that our articles meet these high standards.Perspective articles provide a forum for viewpoints and opinionated discussions of a field or topic, describe historical foundations and influence, emerging research trends and techniques, and ethical, legal and societal issues. These articles are targeted towards readers from advanced undergraduate level and upwards and should be accessible to readers working in any discipline.Please submit your report in narrative form and provide detailed justifications for all statements. Confidential comments to the editor are welcome, but it is helpful if the main points are stated in the comments for transmission to the authors.Please note that all Nature Reviews articles will be thoroughly edited before publication and all figures will be redrawn by our in-house art editors. We therefore request that you concentrate on the scientific content of the article, rather than any minor errors in language or grammar.

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Section: Genetic Predispositionmentioning

confidence: 90%

Association of metabolic dysfunction-associated fatty liver disease with kidney disease

Wang

et al. 2022

Nat Rev Nephrol

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107

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“…As CKD is a risk factor for MAFLD, 10 we also examined the association between the MAFLD‐CKD and the risk of having PNPLA3 and HSD17B13 genetic variants 34,35 . The risk alleles of the PNPLA3 rs738409 and HSD17B 13 rs72613567 genotypes were in the Hardy–Weinberg equilibrium ( p = .82 and p = .73).…”

Section: Resultsmentioning

confidence: 99%

Serum PRO‐C3 is useful for risk prediction and fibrosis assessment in MAFLD with chronic kidney disease in an Asian cohort

Tang,

Sun,

Song

et al. 2024

Liver International

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BackgroundMetabolic dysfunction‐associated fatty liver disease (MAFLD) is an emerging risk factor for chronic kidney disease (CKD). N‐terminal propeptide of collagen type 3 (PRO‐C3) is a biomarker of advanced fibrosis in MAFLD and PRO‐C3 may be involved in renal fibrosis. We aimed to use PRO‐C3 measurements to generate a new algorithmic score to test the prediction of MAFLD with chronic kidney disease (MAFLD–CKD).MethodsA derivation and independent validation cohort of 750 and 129 Asian patients with biopsy‐confirmed MAFLD were included. Serum PRO‐C3 concentration was measured and regression analyses were performed to examine associations with MAFLD–CKD. A derivative algorithm for MAFLD–CKD risk prediction was evaluated with receiver operator characteristic (ROC) curve analysis.ResultsThe study included two Asian cohorts (n = 180 with MAFLD–CKD; mean‐eGFR: 94.93 mL/min/1.73 m2; median‐urinary albumin‐to‐creatinine ratio: 6.58 mg/mmol). PRO‐C3 was associated with the severity of MAFLD‐CKD and independently associated with MAFLD–CKD (adjusted odds ratio = 1.16, 95% confidence interval [CI]: 1.08–1.23, p < .001). A new non‐invasive score (termed PERIOD) including PRO‐C3 efficiently predicted MAFLD‐CKD (AUROC = .842, 95% CI: .805–.875). Accuracy, specificity and negative predictive values were 80.2%, 85.1% and 88.4%, respectively. In the validation cohort, the PERIOD score had good diagnostic performance (AUROC = .807, 95% CI: .691–.893) with similar results in all patient subgroups. In the MAFLD–CKD subgroup, the accuracy for identifying advanced fibrosis was further improved by combining the PRO‐C3‐based ADAPT with the Agile 3+ scores (AUROC = .90, 95% CI: .836–.964).ConclusionsThe PERIOD score is helpful for accurately predicting the risk of MAFLD–CKD. PRO‐C3 can also be used to assess liver fibrosis in people with MAFLD–CKD.

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“…Worldwide prevalence of HSD17B13 rs72613567 minor allele in patients with NAFLD. Data based on MAF in patients with NAFLD are as follows: Argentina, data from Pirola 79 ; Austria, calculated from genotype frequency 111 ; China, data from Sun 77 ; Finland, calculated from genotype frequency 55 ; Germany, calculated from genotype frequency 111 ; Italy, data from Anstee 25 ; Malaysia, data from Ting 86 ; South Korea, data from Koo 112 ; Switzerland, calculated from genotype frequency 111 ; US, data from Serper 78 . MAF, minor allele frequency…”

Section: Global Prevalence Of Hsd17b13 Variantsmentioning

confidence: 99%

“…Data regarding the minor allele frequency of rs72613567 in NAFLD patients are limited. The prevalence of this risk‐reducing variant among NAFLD patients is highest in China (34%), 77 followed by the USA (27%), 78 and the least common in Argentina (16%) (Figure 3). 79 It is less frequent in Hispanic patients (9%) compared to non‐Hispanic patients (23%) with NAFLD in the USA 80 …”

Section: Global Prevalence Of Hsd17b13 Variantsmentioning

confidence: 99%

Review article: the role of HSD17B13 on global epidemiology, natural history, pathogenesis and treatment of NAFLD

Amangurbanova

Huang

Loomba

2022

Aliment Pharmacol Ther

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Background: Non-alcoholic fatty liver disease (NAFLD) occurs in around a quarter of the global population and is one of the leading causes of chronic liver disease. The phenotypic manifestation and the severity of NAFLD are influenced by an interplay of environmental and genetic factors. Recently, several inactivating variants in the novel 17-Beta hydroxysteroid dehydrogenase 13 (HSD17B13) gene have been found to be associated with a reduced risk of chronic liver diseases, including NAFLD. Aims:To review the existing literature on the epidemiology of HSD17B13 and discuss its role in the natural history, disease pathogenesis and treatment of NAFLD. Methods:We extensively searched relevant literature in PubMed, Google Scholar, clini caltr ials.gov and the reference list of articles included in the review.Results: HSD17B13 is a liver-specific, lipid droplet (LD)-associated protein that has enzymatic pathways involving steroids, pro-inflammatory lipid mediators and retinol.The estimated prevalence of the best characterised HSD17B13 variant (rs72613567) ranges from 5% in Africa to 34% in East Asia. Loss-of-function variants in HSD17B13 are protective against the progression of NAFLD from simple steatosis to nonalcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis and hepatocellular carcinoma. Emerging data from mechanistic and preclinical studies with RNA interference (RNAi) and small molecule agents indicate that inhibiting HSD17B13 activity may prevent NAFLD progression. Conclusions:The loss-of-function polymorphisms of the newly identified HSD17B13 gene mitigate the progression of NAFLD. It is important to understand the exact mechanism by which these variants exert a protective effect and implement the gathered knowledge in the treatment of NAFLD.

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The HSD17B13 rs72613567 variant is associated with lower levels of albuminuria in patients with biopsy-proven nonalcoholic fatty liver disease

Cited by 14 publications

References 42 publications

Association of metabolic dysfunction-associated fatty liver disease with kidney disease

Association of metabolic dysfunction-associated fatty liver disease with kidney disease

Serum PRO‐C3 is useful for risk prediction and fibrosis assessment in MAFLD with chronic kidney disease in an Asian cohort

Review article: the role of HSD17B13 on global epidemiology, natural history, pathogenesis and treatment of NAFLD

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