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Hepatitis B genetics

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https://www.readbyqxmd.com/read/29684791/the-role-of-promyelocytic-leukemia-protein-in-steatosis-associated-hepatic-tumors-related-to-chronic-hepatitis-b-virus-infection
#1
Yih-Lin Chung, Mei-Ling Wu
The persistence of hepatitis B surface antigen (HBsAg) is a risk factor for the development of steatosis-associated tumors in chronic hepatitis B virus (HBV) infection, yet little is known about the metabolic link with this factor. We correlated HBV-related pathogenesis in genetically engineered mice and human carriers with metabolic proteomics and lipogenic gene expression profiles. The immunohistochemistry showed that the promyelocytic leukemia protein (PML, a tumor suppressor involved in genome maintenance and fatty acid oxidation), being inversely influenced by the dynamic HBsAg levels from acute phase to seroclearance, appeared as a lipo-metabolic switch linking HBsAg-induced steatosis (lipogenesis) to HBsAg-lost fat-burning hepatocarcinogenesis (lipolysis)...
April 20, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29681852/genotypic-and-phenotypic-factors-influencing-drug-response-in-mexican-patients-with-type-2-diabetes-mellitus
#2
Hector E Sanchez-Ibarra, Luisa M Reyes-Cortes, Xian-Li Jiang, Claudia M Luna-Aguirre, Dionicio Aguirre-Trevino, Ivan A Morales-Alvarado, Rafael B Leon-Cachon, Fernando Lavalle-Gonzalez, Faruck Morcos, Hugo A Barrera-Saldaña
The treatment of Type 2 Diabetes Mellitus (T2DM) consists primarily of oral antidiabetic drugs (OADs) that stimulate insulin secretion, such as sulfonylureas (SUs) and reduce hepatic glucose production (e.g., biguanides), among others. The marked inter-individual differences among T2DM patients' response to these drugs have become an issue on prescribing and dosing efficiently. In this study, fourteen polymorphisms selected from Genome-wide association studies (GWAS) were screened in 495 T2DM Mexican patients previously treated with OADs to find the relationship between the presence of these polymorphisms and response to the OADs...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29671945/the-rs4686434-variant-in-the-fetub-locus-is-associated-with-intrahepatic-triglyceride-content-in-obese-chinese-adults
#3
Zhibin Li, Mingzhu Lin, Changqin Liu, Zheng Chen, Dongmei Wang, Xiulin Shi, Shuyu Yang, Xuejun Li
BACKGROUND: We aimed to explore associations of genetic variants in FETUB locus with intrahepatic triglyceride (IHTG) content. METHODS: We genotyped 4 tagging single-nucleotide polymorphisms (SNPs) of FETUB locus as well as PNPLA3 rs738409 and TM6SF2 rs58542926 in 418 obese Chinese adults who were measured on serum Fetuin-B and IHTG content. RESULTS: Subjects carrying the minor allele G for FETUB rs4686434 showed decreased serum Fetuin-B (AG/GG v...
April 19, 2018: Journal of Diabetes
https://www.readbyqxmd.com/read/29666149/genetic-and-phenotypic-difference-in-cd8-t-cell-exhaustion-between-chronic-hepatitis-b-infection-and-hepatocellular-carcinoma
#4
Xiaochen Wang, Qifeng He, Haiyuan Shen, Xiao-Jie Lu, Beicheng Sun
BACKGROUND: Several recent studies published have suggested that T cell exhaustion exists both in chronic infection and cancer. However, to date, few studies have investigated their differences. Here we designed this study to explore the genetic and phenotypic difference in CD8+ T cell exhaustion between chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC). METHODS: In this study, we assayed the phenotypes and functional states of CD8+ T cells separating from human CHB tissues and HCC tissues, and re-analyse the single-cell sequencing data (GSE98638) published previously...
April 17, 2018: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29660219/hepatitis-b-virus-infection-in-taiwan-the-role-of-ntcp-rs2296651-variant-in-relation-to-sex
#5
Oswald Ndi Nfor, Ming-Fang Wu, Tonmoy Debnath, Chun-Te Lee, Wang Lee, Wen-Hsiu Liu, Disline Manli Tantoh, Shu-Yi Hsu, Yung-Po Liaw
Sodium taurocholate co-transporting polypeptide (NTCP) is a functional receptor for hepatitis B virus infection. NTCP rs2296651 is believed to be an Asian-specific variant responsible for HBV susceptibility. We investigated the relationship between rs2296651 and HBV infection in Taiwan based on stratification by gender and menopausal status. We recruited 10017 Taiwan Biobank participants aged 30-70 years with complete genetic data and sociodemographic information. Gender-stratified multivariate logistic regression models were used to determine the relationship between NTCP variant and HBV infection...
April 16, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29656147/liver-fibrosis-direct-antifibrotic-agents-and-targeted-therapies
#6
REVIEW
Detlef Schuppan, Muhammad Ashfaq-Khan, Ai Ting Yang, Yong Ook Kim
Liver fibrosis and in particular cirrhosis are the major causes of morbidity and mortality of patients with chronic liver disease. Their prevention or reversal have become major endpoints in clinical trials with novel liver specific drugs. Remarkable progress has been made with therapies that efficiently address the cause of the underlying liver disease, as in chronic hepatitis B and C. Highly effective antiviral therapy can prevent progression or even induce reversal in the majority of patients, but such treatment remains elusive for the majority of liver patients with advanced alcoholic or nonalcoholic steatohepatitis, genetic or autoimmune liver diseases...
April 12, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29627528/the-association-between-donor-genetic-variations-in-one-carbon-metabolism-pathway-genes-and-hepatitis-b-recurrence-after-liver-transplantation
#7
Di Lu, Jianyong Zhuo, Modan Yang, Chao Wang, Pan Linhui, Haiyang Xie, Xiao Xu, Shusen Zheng
BACKGROUNDS AND AIM: Hepatitis B recurrence adversely affects patients' survival after liver transplantation. This study aims to find association between donor gene variations of one carbon metabolism and post-transplant hepatitis B recurrence. METHODS: This study enrolled 196 patients undergoing liver transplantation for HBV related end-stage liver diseases. We detected 11 single nucleotide polymorphisms (SNP) of 7 one-carbon metabolism pathway genes (including MTHFR, MTR, MTRR, ALDH1L1, GART, SHMT1 and CBS) in donor livers and analyzed their association with HBV reinfection after liver transplantation...
April 5, 2018: Gene
https://www.readbyqxmd.com/read/29619113/analysis-of-circulating-angiopoietin-like-protein-3-and-genetic-variants-in-lipid-metabolism-and-liver-health-the-diogenes-study
#8
Anne Lundby Hess, Jérôme Carayol, Trine Blædel, Jörg Hager, Alessandro Di Cara, Arne Astrup, Wim H M Saris, Lesli Hingstrup Larsen, Armand Valsesia
Background: Angiopoietin-like protein 3 (ANGPTL3), a liver-derived protein, plays an important role in the lipid and lipoprotein metabolism. Using data available from the DiOGenes study, we assessed the link with clinical improvements (weight, plasma lipid, and insulin levels) and changes in liver markers, alanine aminotransferase, aspartate aminotransferase (AST), adiponectin, fetuin A and B, and cytokeratin 18 (CK-18), upon low-calorie diet (LCD) intervention. We also examined the role of genetic variation in determining the level of circulating ANGPTL3 and the relation between the identified genetic markers and markers of hepatic steatosis...
2018: Genes & Nutrition
https://www.readbyqxmd.com/read/29596577/rare-scarb1-mutations-associate-with-high-density-lipoprotein-cholesterol-but-not-with-coronary-artery-disease
#9
Anna Helgadottir, Patrick Sulem, Gudmundur Thorgeirsson, Solveig Gretarsdottir, Gudmar Thorleifsson, Brynjar Ö Jensson, Gudny A Arnadottir, Isleifur Olafsson, Gudmundur I Eyjolfsson, Olof Sigurdardottir, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Hilma Holm, Kari Stefansson
Aims: Scavenger receptor Class B Type 1 (SR-BI) is a major receptor for high-density lipoprotein (HDL) that promotes hepatic uptake of cholesterol from HDL. A rare mutation p.P376L, in the gene encoding SR-BI, SCARB1, was recently reported to associate with elevated HDL cholesterol (HDL-C) and increased risk of coronary artery disease (CAD), suggesting that increased HDL-C caused by SR-BI impairment might be an independent marker of cardiovascular risk. We tested the hypothesis that alleles in or close to SCARB1 that associate with elevated levels of HDL-C also associate with increased risk of CAD in the relatively homogeneous population of Iceland...
March 27, 2018: European Heart Journal
https://www.readbyqxmd.com/read/29589101/regression-of-human-cirrhosis-an-update-18-years-after-the-pioneering-article-by-wanless-et-al
#10
REVIEW
Prodromos Hytiroglou, Neil D Theise
Cirrhosis has been traditionally viewed as an irreversible, end-stage condition. Eighteen years ago, Wanless, Nakashima, and Sherman published a study that was based on the concept that hepatic architecture is under constant remodeling in the course of chronic liver diseases, even during their most advanced stages; depending on the balance between injury and repair, the histologic changes might be progressing or regressing. These authors described in detail the morphologic features of regressing cirrhosis, identified a set of histologic features of regression that they called the "hepatic repair complex," and provided convincing morphologic evidence that incomplete septal cirrhosis represents regressed cirrhosis...
March 27, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29582521/identified-oas3-gene-variants-associated-with-coexistence-of-hbsag-and-anti-hbs-in-chronic-hbv-infection
#11
Sa Wang, Jing Wang, Mengjie Fan, Tengyan Li, Hong Pan, Xi Wang, Hankui Liu, Qiongfen Lin, Jianguo Zhang, Liping Guan, Daria V Zhernakova, Stephen J O'Brien, Zhenru Feng, Le Chang, Erhei Dai, Jianhua Lu, Hongli Xi, Zheng Zeng, Yanyan Yu, Binbin Wang
The underlying mechanism of coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antigen antibody (anti-HBs) is still controversial. To identify the host genetic factors related to this unusual clinical phenomenon, a two-staged study was conducted in the Chinese Han population. In the first stage, we performed a case-control (1:1) age, gender matched study of 101 cases with concurrent HBsAg and anti-HBs and 102 controls with negative HBsAg and positive anti-HBs using whole exome sequencing...
March 27, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29579787/significant-snps-related-to-telomere-length-and-hepatocellular-carcinoma-risk-in-chronic-hepatitis-b-carriers
#12
Ashraf Mohamadkhani, Masoumeh Pourasgari, Hossein Poustchi
Chronic hepatitis B virus (HBV) infection increases the risk of developing cirrhosis and hepatocellular carcinoma (HCC) with suspected interactions between virus replication and host immune responses. A number of reports have suggested that telomerase function may be involved in chronic hepatitis B (CHB) pathogenesis, but positive or negative associations with HCC risk remain for discussion. Mean telomere length is an indicator of biological aging and it has been reported that reduction in NBV carriers compared to normal individuals...
March 27, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29579736/metformin-reduces-glucose-intolerance-caused-by-rapamycin-treatment-in-genetically-heterogeneous-female-mice
#13
Roxanne Weiss, Elizabeth Fernandez, Yuhong Liu, Randy Strong, Adam B Salmon
The use of rapamycin to extend lifespan and delay age-related disease in mice is well-established despite its potential to impair glucose metabolism which is driven partially due to increased hepatic gluconeogenesis. We tested whether a combination therapeutic approach using rapamycin and metformin could diminish some of the known metabolic defects caused by rapamycin treatment in mice. In genetically heterogeneous HET3 mice, we found that chronic administration of encapsulated rapamycin by diet caused a measurable defect in glucose metabolism in both male and female mice as early as 1 month after treatment...
March 22, 2018: Aging
https://www.readbyqxmd.com/read/29576871/-de-novo-hnf1-homeobox-b-mutation-as-a-cause-for-chronic-treatment-resistant-hypomagnesaemia
#14
C E Stiles, R Thuraisingham, D Bockenhauer, L Platts, A V Kumar, M Korbonits
29-year-old female presenting with an 8-year history of unexplained hypomagnesaemia, which was severe enough to warrant intermittent inpatient admission for intravenous magnesium. Urinary magnesium was inappropriately normal in the context of hypomagnesaemia indicating magnesium wasting. Ultrasound imaging demonstrated unilateral renal cysts and computed tomography of kidneys, ureters and bladder showed a bicornuate uterus. Referral to genetic services and subsequent testing revealed a de novo HNF1B deletion...
2018: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29572891/novel-link-between-gut-microbiome-derived-metabolite-and-shared-gene-effects-with-hepatic-steatosis-and-fibrosis-in-nafld
#15
Cyrielle Caussy, Cynthia Hsu, Min-Tzu Lo, Amy Liu, Ricki Bettencourt, Veeral H Ajmera, Shirin Bassirian, Jonathan Hooker, Ethan Sy, Lisa Richards, Nicholas Schork, Bernd Schnabl, David A Brenner, Claude B Sirlin, Chi-Hua Chen, Rohit Loomba
Previous studies have shown that gut-microbiome is associated with nonalcoholic fatty liver disease (NAFLD). We aimed to examine if serum metabolites especially those derived from the gut-microbiome have a shared gene-effect with hepatic steatosis and fibrosis. This is a cross-sectional analysis of a prospective discovery cohort including 156 well-characterized Twins and Families with untargeted metabolome profiling assessment. Hepatic steatosis was assessed using magnetic-resonance-imaging proton-density-fat-fraction (MRI-PDFF) and fibrosis using MR-elastography (MRE)...
March 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29572094/hepatic-targeted-rna-interference-provides-persistent-knockdown-of-alpha-1-antitrypsin-levels-in-zz-patients
#16
Alice M Turner, Jan Stolk, Robert Bals, Jason Lickliter, James Hamilton, Dawn R Christianson, Bruce D Given, Jonathan G Burdon, Rohit Loomba, James K Stoller, Jeffery H Teckman
BACKGROUND & AIMS: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder causing pulmonary and liver disease. The PiZ mutation results in mis-folded alpha-1 antitrypsin protein (Z-AAT) leading to hepatocyte accumulation, fibrosis and cirrhosis. RNAi-based therapeutics silencing production of hepatic Z-AAT might benefit patients with AATD-associated liver disease. This study evaluated an RNAi therapeutic to silence production of alpha-1 antitrypsin. METHODS: Part A of this double-blind first-in-human study randomized 54 healthy volunteers (HVs) into single dose cohorts (2 placebo: 4 active), receiving escalating doses of the investigational agent ARC-AAT from 0...
March 20, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29566006/early-minion%C3%A2-nanopore-single-molecule-sequencing-technology-enables-the-characterization-of-hepatitis-b-virus-genetic-complexity-in-clinical-samples
#17
Virginie Sauvage, Laure Boizeau, Daniel Candotti, Mathias Vandenbogaert, Annabelle Servant-Delmas, Valérie Caro, Syria Laperche
Until recently, the method of choice to characterize viral diversity consisted in cloning PCR amplicons of full-length viral genomes and Sanger-sequencing of multiple clones. However, this is extremely laborious, time-consuming, and low-throughput. Next generation short-read sequencing appears also limited by its inability to directly sequence full-length viral genomes. The MinION™ device recently developed by Oxford Nanopore Technologies can be a promising alternative by applying long-read single-molecule sequencing directly to the overall amplified products generated in a PCR reaction...
2018: PloS One
https://www.readbyqxmd.com/read/29562163/a-protein-truncating-hsd17b13-variant-and-protection-from-chronic-liver-disease
#18
Noura S Abul-Husn, Xiping Cheng, Alexander H Li, Yurong Xin, Claudia Schurmann, Panayiotis Stevis, Yashu Liu, Julia Kozlitina, Stefan Stender, G Craig Wood, Ann N Stepanchick, Matthew D Still, Shane McCarthy, Colm O'Dushlaine, Jonathan S Packer, Suganthi Balasubramanian, Nehal Gosalia, David Esopi, Sun Y Kim, Semanti Mukherjee, Alexander E Lopez, Erin D Fuller, John Penn, Xin Chu, Jonathan Z Luo, Uyenlinh L Mirshahi, David J Carey, Christopher D Still, Michael D Feldman, Aeron Small, Scott M Damrauer, Daniel J Rader, Brian Zambrowicz, William Olson, Andrew J Murphy, Ingrid B Borecki, Alan R Shuldiner, Jeffrey G Reid, John D Overton, George D Yancopoulos, Helen H Hobbs, Jonathan C Cohen, Omri Gottesman, Tanya M Teslovich, Aris Baras, Tooraj Mirshahi, Jesper Gromada, Frederick E Dewey
BACKGROUND: Elucidation of the genetic factors underlying chronic liver disease may reveal new therapeutic targets. METHODS: We used exome sequence data and electronic health records from 46,544 participants in the DiscovEHR human genetics study to identify genetic variants associated with serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Variants that were replicated in three additional cohorts (12,527 persons) were evaluated for association with clinical diagnoses of chronic liver disease in DiscovEHR study participants and two independent cohorts (total of 37,173 persons) and with histopathological severity of liver disease in 2391 human liver samples...
March 22, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29558758/the-influence-of-b-and-t-lymphocyte-attenuator-genetic-variants-on-susceptibility-to-chronic-hepatitis-b-virus-infection
#19
Jie Tang, Jiaqian Fei, Chunxia Gu, Weixia Liu, Minwei Li, Cheng Zhou
BACKGROUND/AIMS: B and T lymphocyte attenuator (BTLA) is an immune inhibitory receptor involved in the pathogenesis of chronic viral infections. Little is known about the effects of BTLA gene polymorphisms on chronic hepatitis B virus (HBV) infections. In this study, we investigated whether the polymorphisms of BTLA are associated with the progression of chronic HBV infection. METHODS: A total of 382 chronic HBV carriers and 170 healthy individuals in the same region were recruited for this study...
March 16, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29558354/-the-changing-face-of-medium-sized-vasculitis
#20
Jolanta Parada-Turska, Monika Turska
Polyarteritis nodosa is a systemic necrotizing vasculitis which predominantly affects medium-sized arteries. It is a rare disease nowadays. Both the nomenclature and the classification of polyarteritis nodosa was amended several times in the past. Currently, there is a distinction between the primary form described as classical polyarteritis nodosa and other forms that are associated with their probable cause e.g. with viral hepatitis B, C or HIV infection. Moreover, polyarteritis-like necrotizing vasculitis can appear in the course of genetic diseases caused by mutations in single genes...
2018: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
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