A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers

Whitfield, John B.; Schwantes‐An, Tae‐Hwi; Darlay, Rebecca; Aithal, Guruprasad P.; Atkinson, Stephen R.; Bataller, Ramón; Botwin, Greg; Chalasani, Naga; Cordell, Heather J.; Daly, Ann K.; Day, Christopher P.; Eyer, Florian; Foroud, Tatiana; Gleeson, Dermot; Goldman, David; Haber, Paul; Jacquet, Jean‐Marc; Liang, Tiebing; Liangpunsakul, Suthat; Masson, Steven; Maury, Philippe; Moirand, Romain; McQuillin, Andrew; Moreno, Christophe; Morgan, Marsha Y.; Mueller, Sebastian; Müllhaupt, Beat; Nagy, Laura E.; Nahon, Pierre; Nalpas, Bertrand; Naveau, Sylvie; Perney, Pascal; Pirmohamed, Munir; Seitz, Helmut K.; Soyka, Michael; Stickel, Felix; Thompson, Andrew; Thursz, Mark; Trépo, Eric; Morgan, Timothy R.; Seth, Devanshi

doi:10.1016/j.jhep.2021.10.005

Cited by 45 publications

(27 citation statements)

References 36 publications

(43 reference statements)

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“…In a case-control study including 769 ALD patients and 767 healthy controls, the HSD17B13 rs72613567:TA allele was associated with a decreased risk of ALD by 19% (Chen et al, 2020). Furthermore, a combination of another HSD17B13:rs68343143 variant and two other genetic variants (PNPLA3:rs738409 and TM6SF2:rs10401969) can predict the development of alcohol-related cirrhosis in heavy drinkers (Whitfield et al, 2021). Importantly, the risk of hepatocellular carcinoma was also decreased in patients heterozygous (OR 0.65) and homozygous (OR 0.28) for the HSD17B13 rs72613567:TA allele (Abul-Husn et al, 2018).…”

Section: Hsd17b13 Snps In Other Chronic Liver Diseasesmentioning

confidence: 99%

HSD17B13: A Potential Therapeutic Target for NAFLD

Zhang

et al. 2022

Front. Mol. Biosci.

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Nonalcoholic fatty liver disease (NAFLD), especially in its inflammatory form (steatohepatitis, NASH), is closely related to the pathogenesis of chronic liver disease. Despite substantial advances in the management of NAFLD/NASH in recent years, there are currently no efficacious therapies for its treatment. The biogenesis and expansion of lipid droplets (LDs) are critical pathophysiological processes in the development of NAFLD/NASH. In the past decade, increasing evidence has demonstrated that lipid droplet-associated proteins may represent potential therapeutic targets for the treatment of NAFLD/NASH given the critical role they play in regulating the biogenesis and metabolism of lipid droplets. Recently, HSD17B13, a newly identified liver-enriched, hepatocyte-specific, lipid droplet-associated protein, has been reported to be strongly associated with the development and progression of NAFLD/NASH in both mice and humans. Notably, human genetic studies have repeatedly reported a robust association of HSD17B13 single nucleotide polymorphisms (SNPs) with the occurrence and severity of NAFLD/NASH and other chronic liver diseases (CLDs). Here we briefly overview the discovery, tissue distribution, and subcellular localization of HSD17B13 and highlight its important role in promoting the pathogenesis of NAFLD/NASH in both experimental animal models and patients. We also discuss the potential of HSD17B13 as a promising target for the development of novel therapeutic agents for NAFLD/NASH.

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Section: Hsd17b13 Snps In Other Chronic Liver Diseasesmentioning

confidence: 99%

HSD17B13: A Potential Therapeutic Target for NAFLD

Zhang

et al. 2022

Front. Mol. Biosci.

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“…The weak effects of single SNPs on disease risk have greatly limited their clinical translation. Encouragingly, accumulating evidence has indicated that risk scores derived from a panel of disease-causing SNPs are promising markers [ 38 , 39 ]. Cuzick et al demonstrated that the SNP88 risk score was predictive of breast cancer risk and substantially improved risk predictive accuracy when combined with the existing breast cancer risk assessment tool Tyrer-Cuzick (TC) [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…Cuzick et al demonstrated that the SNP88 risk score was predictive of breast cancer risk and substantially improved risk predictive accuracy when combined with the existing breast cancer risk assessment tool Tyrer-Cuzick (TC) [ 38 ]. In addition, the Whitfield group reported that a genetic risk score based on 3 SNPs and diabetes status could robustly discriminate cirrhosis risk [ 39 ]. Therefore, it is essential to identify more hepatoblastoma susceptibility to develop risk prediction panels of polygenic SNPs.…”

Section: Discussionmentioning

confidence: 99%

METTL1 gene polymorphisms synergistically confer hepatoblastoma susceptibility

Zhu

Liu

et al. 2022

Discov Onc

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Introduction Hepatoblastoma is a rare but devastating pediatric liver malignancy. Overexpressed methyltransferase-like 1 (METTL1) is a methyltransferase that catalyzes essential N7-methylguanosine (m7G) modification of eukaryotic mRNA. Accumulating evidence has revealed the oncogenic potential of METTL1. However, whether METTL1 gene polymorphisms confer susceptibility to hepatoblastoma has not been reported. This study aimed to identify causal relationships between genetic variants of this gene and susceptibility to hepatoblastoma. Materials and methods Using the TaqMan assay, we genotyped three METTL1 polymorphisms (rs2291617 G > T, rs10877013 T > C, rs10877012 T > G) in germline DNA samples from 1759 Chinese children of Han ethnicity (313 cases vs. 1446 controls). Results None of these polymorphisms were associated with hepatoblastoma risk. However, combination analysis showed that children with 1 to 3 risk genotypes were associated with increased hepatoblastoma risk (adjusted odds ratio = 1.47, 95% confidence interval 1.07–2.02; P = 0.018). Stratified analyses revealed significant effects of combined polymorphisms mainly among young children (< 17 months of age), boys, and those with advanced hepatoblastoma. Conclusion We identified some potential functional METTL1 gene polymorphisms that work together to increase the risk of hepatoblastoma among Chinese Han children; single polymorphism showed only weak effects. These METTL1 polymorphisms may be promising biomarkers for screening high-risk individuals for hepatoblastoma. These findings are inspiring and deserve to be validated among individuals of different ethnicities. Graphical Abstract

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“…In this landmark retrospective, registry-based multicentric cohort study spanning four continents, the authors evaluated 3,380 adults with a clinical and/or histological diagnosis of alcoholic hepatitis (AH). 1 The clinical definition of AH was as per the National Institute on Alcohol Abuse and Alcoholism. 2 Corticosteroids are the only effective therapy for severe alcoholic hepatitis (sAH), defined by a model for end-stage liver disease (MELD) score >20.…”

Section: Discussionmentioning

confidence: 99%

A Genetic Risk Score and Diabetes Predict the Development of Alcohol-Related Cirrhosis in Drinkers!

2022

Journal of Clinical and Experimental Hepatology

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A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers

Cited by 45 publications

References 36 publications

HSD17B13: A Potential Therapeutic Target for NAFLD

HSD17B13: A Potential Therapeutic Target for NAFLD

METTL1 gene polymorphisms synergistically confer hepatoblastoma susceptibility

A Genetic Risk Score and Diabetes Predict the Development of Alcohol-Related Cirrhosis in Drinkers!

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