HSD17B13 as a promising therapeutic target against chronic liver disease

Stender, Stefan; Romeo, Stefano

doi:10.1111/liv.14411

Cited by 10 publications

(13 citation statements)

References 22 publications

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“…20 Recent findings have demonstrated that selective targeting of HSD17B13 mRNA in hepatocytes might be a promising therapeutic approach in NASH. 35,36 Although the HSD17B13 variant did not modify liver phenotypes in our patients, it affected testosterone and SHBG levels in the Polish and German cohorts respectively. A similar finding i.e., a lower testosterone levels, was previously described in male patients with advanced chronic liver disease.…”

Section: Discussioncontrasting

confidence: 54%

Liver phenotypes in PCOS: Analysis of exogenous and inherited risk factors for liver injury in two European cohorts

Smyk

Papapostoli

Żorniak

et al. 2023

Liver International

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Background & Aims: Fatty liver disease (FLD) is common in women with polycystic ovary syndrome (PCOS). Here, we use non-invasive tests to quantify liver injury in women with PCOS and analyse whether FLD-associated genetic variants contribute to liver phenotypes in PCOS.Methods: Prospectively, we recruited women with PCOS and controls at two university centres in Germany and Poland. Alcohol abuse was regarded as an exclusion criterion. Genotyping of variants associated with FLD was performed using TaqMan How to cite this article: Smyk W, Papapostoli I, Żorniak M, et al. Liver phenotypes in PCOS: Analysis of exogenous and inherited risk factors for liver injury in two European cohorts.

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Section: Discussioncontrasting

confidence: 54%

Liver phenotypes in PCOS: Analysis of exogenous and inherited risk factors for liver injury in two European cohorts

Smyk

Papapostoli

Żorniak

et al. 2023

Liver International

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“…The present study is the first extending the association between HSD17B13 and protection against chronic liver disease to an Asian population, namely Pakistani. Our data are consistent with those reported for other ethnicities and, together with them, underline the potential of HSD17B13 as a therapeutic target [41] to treat liver disease irrespective of ethnicity, and its role in the genetic susceptibility to chronic liver disease.…”

Section: Discussionsupporting

confidence: 92%

Genetic Susceptibility to Chronic Liver Disease in Individuals from Pakistan

Raja

Ciociola

Ahmad

et al. 2020

IJMS

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Chronic liver disease, with viral or non-viral etiology, is endemic in many countries and is a growing burden in Asia. Among the Asian countries, Pakistan has the highest prevalence of chronic liver disease. Despite this, the genetic susceptibility to chronic liver disease in this country has not been investigated. We performed a comprehensive analysis of the most robustly associated common genetic variants influencing chronic liver disease in a cohort of individuals from Pakistan. A total of 587 subjects with chronic liver disease and 68 healthy control individuals were genotyped for the HSD17B13 rs7261356, MBOAT7 rs641738, GCKR rs1260326, PNPLA3 rs738409, TM6SF2 rs58542926 and PPP1R3B rs4841132 variants. The variants distribution between case and control group and their association with chronic liver disease were tested by chi-square and binary logistic analysis, respectively. We report for the first time that HSD17B13 variant results in a 50% reduced risk for chronic liver disease; while MBOAT7; GCKR and PNPLA3 variants increase this risk by more than 35% in Pakistani individuals. Our genetic analysis extends the protective role of the HSD17B13 variant against chronic liver disease and disease risk conferred by the MBOAT7; GCKR and PNPLA3 variants in the Pakistani population.

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“…Therefore, it is desirable to investigate the underlying mechanisms of lean NAFLD and provide advice for its treatment and related drug development. As a protective allele for various liver diseases, HSD17B13 rs72613567 is considered to be an attractive target for therapeutic drug development [38,39]. Our results here showed that the effect of HSD17B13 rs72613567 in lean NAFLD differs from that in non-lean NAFLD, which implications for drug development and personalized treatment for lean NAFLD.…”

Section: Discussionmentioning

confidence: 64%

Genetic variation of HSD17B13 is associated with an increased risk of lean nonalcoholic fatty liver disease

Hong

Zhang

et al. 2022

Preprint

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Background/purpose: Carriage of HSD17B13 rs72613567:TA is associated with a reduced risk of nonalcoholic fatty liver disease (NAFLD); however, whether this protective effect exists in lean NAFLD remains unknown. Therefore, we compared the association of HSD17B13 rs72613567 and NAFLD between lean and non-lean individuals.Methods: We tested the association of HSD17B13 rs72613567 with NAFLD, cirrhosis, and hepatocellular carcinoma (HCC) in 313,309 individuals from the UK Biobank, including 1464 patients with NAFLD, 1559 with cirrhosis, and 526 with HCC. We calculated the minor allele frequency (MAF) of HSD17B13 rs72613567 and analyzed this SNP using codominant, dominant, and recessive models. Furthermore, we calculated the population-attributable fraction (PAF) and the combined PAF for five SNPs (HSD17B13 rs72613567, TM6SF2 rs58542926, MBOAT7 rs641738, PNPLA3 rs738409, and GCKR rs1260326) and used multifactor dimensionality reduction (MDR) to analyze the interactions between HSD17B13 and the other four SNPs. Results: The MAF of HSD17B13 rs72613567 was considerably higher in lean NAFLD (32.57%) than in non-lean NAFLD (26.16%). Moreover, homozygosity of the TA allele showed a significant risk effect in the codominant (OR = 1.94; 95% CI: 1.09–3.44) and recessive models (OR = 1.94; 95% CI: 1.12–3.35). By contrast, in the case of cirrhosis, HCC, and non-lean NAFLD, both homozygosity and heterozygosity of the TA allele showed a protective effect. Finally, the MDR analysis did not detect any interaction between HSD17B13 and the other four SNPs. Conclusion: The polymorphism of HSD17B13 rs72613567 is different between lean and non-lean NAFLD, and the TA allele showed a risk effect for lean NAFLD.

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HSD17B13 as a promising therapeutic target against chronic liver disease

Abstract: See Article on Page 889

Cited by 10 publications

References 22 publications

Liver phenotypes in PCOS: Analysis of exogenous and inherited risk factors for liver injury in two European cohorts

Liver phenotypes in PCOS: Analysis of exogenous and inherited risk factors for liver injury in two European cohorts

Genetic Susceptibility to Chronic Liver Disease in Individuals from Pakistan

Genetic variation of HSD17B13 is associated with an increased risk of lean nonalcoholic fatty liver disease

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