Chronic liver disease(CLD)represents a significant global health burden,with hepatic steatosis-associated disorders—such as metabolic dysfunction-associated steatohepatitis(MASH),alcoholic liver disease,and hepatitis...Chronic liver disease(CLD)represents a significant global health burden,with hepatic steatosis-associated disorders—such as metabolic dysfunction-associated steatohepatitis(MASH),alcoholic liver disease,and hepatitis C virus infection—being major contributors.Recent genome-wide association studies have identified the rs72613567:TA variant in the 17-beta-hydroxysteroid dehydrogenase 13(HSD17B13)gene as a protective factor against the development and progression of these conditions.In this review,we summarized the current evidence surrounding the HSD17B13 rs72613567 variant,aiming to elucidate its impact on CLD risk and outcomes,and to explore the potential mechanisms behind its hepatoprotective effects.The rs72613567:TA variant induces a splice donor site mutation,resulting in a truncated,nonfunctional HSD17B13 protein.Numerous studies have demonstrated that this loss-of-function mutation confers protection against the development of cirrhosis and hepatocellular carcinoma(HCC)in patients with MASH,alcoholic liver disease,and hepatitis C virus infection.Moreover,the rs72613567:TA variant has been associated with reduced liver enzyme levels and improved survival in HCC patients.Integrating this variant into genetic risk scores has shown promise in predicting the progression of fatty liver disease to cirrhosis and HCC.Furthermore,inhibiting HSD17B13 expression through RNA interference and small molecule inhibitors has emerged as a potential therapeutic strategy for MASH.However,the precise molecular mechanisms underlying the hepatoprotective effects of the HSD17B13 rs72613567 variant remain to be fully elucidated.Future research should focus on clarifying the structure-function relationship of HSD17B13 and its role in liver pathophysiology to facilitate the development of targeted therapies for CLD associated with hepatic steatosis.展开更多
Background and Aims:In Europeans,variants in the hydroxysteroid 17-beta dehydrogenase 13(HSD17B13)gene impact liver histology in metabolic-associated fatty liver disease(MAFLD).The impact of these variants in ethnic C...Background and Aims:In Europeans,variants in the hydroxysteroid 17-beta dehydrogenase 13(HSD17B13)gene impact liver histology in metabolic-associated fatty liver disease(MAFLD).The impact of these variants in ethnic Chinese is unknown.The aim of this study was to investigate the potential associations in Chinese patients.Methods:In total,427 Han Chinese with biopsy-confirmed MAFLD were enrolled.Two single nucleotide polymorphisms in HSD17B13 were genotyped:rs72613567 and rs6531975.Logistic regression was used to test the association between the single nucleotide polymorphisms and liver histology.Results:In our cohort,the minor allele TA of the rs72613567 variant was related to an increased risk of fibrosis[odds ratio(OR):2.93(1.20–7.17),p=0.019 for the additive model;OR:3.32(1.39–7.91),p=0.007 for the recessive model],representing an inverse association as compared to the results from European cohorts.In contrast,we observed a protective effect on fibrosis for the minor A allele carriers of the HSD17B13 rs6531975 variant[OR:0.48(0.24–0.98),p=0.043 for the additive model;OR:0.62(0.40–0.94),p=0.025 for the dominant model].HSD17B13 variants were only associated with fibrosis but no other histological features.Furthermore,HSD17B13 rs6531975 modulated the effect of PNPLA3 rs738409 on hepatic steatosis.Conclusions:HSD17B13 rs72613567 is a risk variant for fibrosis in a Han Chinese MAFLD population but with a different direction for allelic association to that seen in Europeans.These data exemplify the need for studying diverse populations in genetic studies in order to fine map genome-wide association studies signals.展开更多
Objective: To investigate the correlation between 17-beta-hydroxysteroid dehydrogenase type1(17β-HSD-1) gene polymorphisms and risk of endometrial adenocarcino-ma.Methods: Forty-one patients with endometrial adenocar...Objective: To investigate the correlation between 17-beta-hydroxysteroid dehydrogenase type1(17β-HSD-1) gene polymorphisms and risk of endometrial adenocarcino-ma.Methods: Forty-one patients with endometrial adenocarcinoma were selected as experimen-tal group and twenty-seven healthy women were selected as control group.The three common single nucleotide polymorphism of 17β-HSD-1 gene at sites + 1004,+ 1322 and + 1954 were detected by allele-specific PCR(ASA-PCR).The allele frequencies were analyzed by SPSS13.0 software between endometrial cancer cases and controls.Results: We observed no significant difference in various frequency distribution between experimental group and control group.P1004= 0.994,P1322 = 0.974,and P1954 = 0.981.Conclusion: We found that three common SNPs with the 17β-HSD-1 gene were not associated with endometrial adenocarcinoma.We suggest that more research for 17β-HSD needs to explore.展开更多
文摘Chronic liver disease(CLD)represents a significant global health burden,with hepatic steatosis-associated disorders—such as metabolic dysfunction-associated steatohepatitis(MASH),alcoholic liver disease,and hepatitis C virus infection—being major contributors.Recent genome-wide association studies have identified the rs72613567:TA variant in the 17-beta-hydroxysteroid dehydrogenase 13(HSD17B13)gene as a protective factor against the development and progression of these conditions.In this review,we summarized the current evidence surrounding the HSD17B13 rs72613567 variant,aiming to elucidate its impact on CLD risk and outcomes,and to explore the potential mechanisms behind its hepatoprotective effects.The rs72613567:TA variant induces a splice donor site mutation,resulting in a truncated,nonfunctional HSD17B13 protein.Numerous studies have demonstrated that this loss-of-function mutation confers protection against the development of cirrhosis and hepatocellular carcinoma(HCC)in patients with MASH,alcoholic liver disease,and hepatitis C virus infection.Moreover,the rs72613567:TA variant has been associated with reduced liver enzyme levels and improved survival in HCC patients.Integrating this variant into genetic risk scores has shown promise in predicting the progression of fatty liver disease to cirrhosis and HCC.Furthermore,inhibiting HSD17B13 expression through RNA interference and small molecule inhibitors has emerged as a potential therapeutic strategy for MASH.However,the precise molecular mechanisms underlying the hepatoprotective effects of the HSD17B13 rs72613567 variant remain to be fully elucidated.Future research should focus on clarifying the structure-function relationship of HSD17B13 and its role in liver pathophysiology to facilitate the development of targeted therapies for CLD associated with hepatic steatosis.
基金This work was supported by grants from the National Natural Science Foundation of China(82070588)High Level Creative Talents from Department of Public Health in Zhejiang Province(S2032102600032)+3 种基金Project of New Century 551 Talent Nurturing in Wenzhou.GT was supported in part by grants from the University School of Medicine of Verona(Verona,Italy)CDB was supported in part by the Southampton NIHR Biomedical Research Centre(ISBRC-20004)UK.ME and JG were supported by the Robert W.Storr Bequest to the Sydney Medical Foundation,University of Sydney(Sydney,Australia)and the National Health and Medical Research Council of Australia(NHMRC)Program(APP1053206,APP1149976)Project(APP1107178 and APP1108422)grants.
文摘Background and Aims:In Europeans,variants in the hydroxysteroid 17-beta dehydrogenase 13(HSD17B13)gene impact liver histology in metabolic-associated fatty liver disease(MAFLD).The impact of these variants in ethnic Chinese is unknown.The aim of this study was to investigate the potential associations in Chinese patients.Methods:In total,427 Han Chinese with biopsy-confirmed MAFLD were enrolled.Two single nucleotide polymorphisms in HSD17B13 were genotyped:rs72613567 and rs6531975.Logistic regression was used to test the association between the single nucleotide polymorphisms and liver histology.Results:In our cohort,the minor allele TA of the rs72613567 variant was related to an increased risk of fibrosis[odds ratio(OR):2.93(1.20–7.17),p=0.019 for the additive model;OR:3.32(1.39–7.91),p=0.007 for the recessive model],representing an inverse association as compared to the results from European cohorts.In contrast,we observed a protective effect on fibrosis for the minor A allele carriers of the HSD17B13 rs6531975 variant[OR:0.48(0.24–0.98),p=0.043 for the additive model;OR:0.62(0.40–0.94),p=0.025 for the dominant model].HSD17B13 variants were only associated with fibrosis but no other histological features.Furthermore,HSD17B13 rs6531975 modulated the effect of PNPLA3 rs738409 on hepatic steatosis.Conclusions:HSD17B13 rs72613567 is a risk variant for fibrosis in a Han Chinese MAFLD population but with a different direction for allelic association to that seen in Europeans.These data exemplify the need for studying diverse populations in genetic studies in order to fine map genome-wide association studies signals.
文摘Objective: To investigate the correlation between 17-beta-hydroxysteroid dehydrogenase type1(17β-HSD-1) gene polymorphisms and risk of endometrial adenocarcino-ma.Methods: Forty-one patients with endometrial adenocarcinoma were selected as experimen-tal group and twenty-seven healthy women were selected as control group.The three common single nucleotide polymorphism of 17β-HSD-1 gene at sites + 1004,+ 1322 and + 1954 were detected by allele-specific PCR(ASA-PCR).The allele frequencies were analyzed by SPSS13.0 software between endometrial cancer cases and controls.Results: We observed no significant difference in various frequency distribution between experimental group and control group.P1004= 0.994,P1322 = 0.974,and P1954 = 0.981.Conclusion: We found that three common SNPs with the 17β-HSD-1 gene were not associated with endometrial adenocarcinoma.We suggest that more research for 17β-HSD needs to explore.
