A new 3p25 locus is associated with liver fibrosis progression in human immunodeficiency virus/hepatitis C virus‐coinfected patients

Ulveling, Damien; Clerc, Sigrid Le; Cobat, Aurélie; Labib, Taoufik; Noirel, Josselin; Laville, Vincent; Coulonges, Cédric; Carpentier, Wassila; Nalpas, Bertrand; Heim, Markus H.; Poynard, Thierry; Cerny, Andreas; Pol, Stanislas; Bochud, Pierre–Yves; Dabis, François; Théodorou, Ioannis; Lévy, Yves; Salmon, Dominique; Abel, Laurent; Dominguez, Stéphanie; Zagury, Jean‐François

doi:10.1002/hep.28695

Cited by 15 publications

(10 citation statements)

References 52 publications

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“…To evaluate the pathological role of the expanded population of MkP in driving bone marrow fibrosis, we next examined potential mediators of fibrosis. Fibrosis regulators were identified from previously published datasets studying lung and liver fibrosis as well as bone marrow fibrosis (Allen et al, 2017;Blackman et al, 2013;Corvol et al, 2015;Gu et al, 2009;Mondet et al, 2015;Mushiroda et al, 2008;Noth et al, 2013;Ulveling et al, 2016;Wattacheril et al, 2017;Wright et al, 2011). Genes detected at expression levels over 1 (using log-transformed UMI) were selected for a 'fibrosis signature' gene score (Suppl.…”

Section: Identifying Mediators Of Megakaryocyte-induced Fibrosismentioning

confidence: 99%

Single-cell analyses reveal aberrant pathways for megakaryocyte-biased hematopoiesis in myelofibrosis and identify mutant clone-specific targets

Psaila

Wang

Rodríguez-Meira

et al. 2019

Preprint

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Myelofibrosis is a severe myeloproliferative neoplasm characterised by increased numbers of abnormal bone marrow megakaryocytes that induce progressive fibrosis, destroying the hematopoietic microenvironment. To determine the cellular and molecular basis for aberrant megakaryopoiesis in myelofibrosis, we performed high-throughput single-cell transcriptome profiling of 50,538 hematopoietic stem/progenitor cells (HSPCs), single-cell proteomics, genomics and functional assays. We identified an aberrant pathway for direct megakaryocyte differentiation from the earliest stages of hematopoiesis in myelofibrosis and associated aberrant molecular signatures, including surface antigens selectively expressed by JAK2-mutant HSPCs. Myelofibrosis megakaryocyte progenitors were heterogeneous, with distinct expression of fibrosis and proliferation-associated genes and putative therapy targets. We validated the immunoglobulin receptor G6B as a promising JAK2-mutant clone-specific antigen warranting further development as 2 an immunotherapy target. Our study paves the way for selective targeting of the myelofibrosis clone and more broadly illustrates the power of single-cell multi-omics to discover tumor-specific therapeutic targets and mediators of tissue fibrosis.

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Section: Identifying Mediators Of Megakaryocyte-induced Fibrosismentioning

confidence: 99%

Single-cell analyses reveal aberrant pathways for megakaryocyte-biased hematopoiesis in myelofibrosis and identify mutant clone-specific targets

Psaila

Wang

Rodríguez-Meira

et al. 2019

Preprint

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“…A range of candidate gene and GWA studies of HIV-related traits have been reported, such as atherosclerosis (Shrestha et al 2010 ), response to antiretroviral drugs (Chantarangsu et al 2011 ; Irvin et al 2011 ; Leger et al 2014 ; Lehmann et al 2015 ), and blood counts in HIV-infected or -exposed patients (Ferreira et al 2010 ; Moore et al 2015 ; Ramsuran et al 2011 ). Similarly HIV-associated diseases have also been interrogated, such as HIV-dementia (Levine et al 2012 ) and hepatitis C (Ulveling et al 2016 ). Although we do not discuss each study in detail here, Supplementary Table 1 provides a recent extract from the GWAS catalog for all HIV and related traits.…”

Section: Introductionmentioning

confidence: 99%

Host genetic variation and HIV disease: from mapping to mechanism

Naranbhai

Carrington

2017

Immunogenetics

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This review aims to provide a summary of current knowledge of host genetic effects on human immunodeficiency virus (HIV) disease. Mapping of simple single nucleotide polymorphisms (SNP) has been largely successful in HIV, but more complex genetic associations involving haplotypic or epigenetic variation, for example, remain elusive. Mechanistic insights explaining SNP associations are incomplete, but continue to be forthcoming. The number of robust immunogenetic correlates of HIV is modest and their discovery mostly predates the genome-wide era. Nevertheless, genome-wide evaluations have nicely validated the impact of HLA and CCR5 variants on HIV disease, and importantly, made clear the many false positive associations that were previously suggested by studies using the candidate gene approach. We describe how multiple HIV outcome measures such as acquisition, viral control, and immune decline have been studied in adults and in children, but that collectively these identify only the two replicable loci responsible for modifying HIV disease, CCR5, and HLA. Recent heritability estimates in this disease corroborate the modest impact of genetic determinants and their oligogenic nature. While the mechanism of protection afforded by genetic variants that diminish CCR5 expression is clear, new aspects of HLA class I-mediated protection continue to be uncovered. We describe how these genetic findings have enhanced insights into immunobiology, been clinically translated into CCR5 antagonists, allowed prioritization of antigens for vaccination efforts, and identified targets for genome-editing interventions. Finally, we describe how studies of genetically complex parts of the genome using new tools may begin revealing additional correlates.Electronic supplementary materialThe online version of this article (doi:10.1007/s00251-017-1000-z) contains supplementary material, which is available to authorized users.

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“…The SNP rs61183828 had a strong association with a genome‐wide level of significance, which was replicated in two independent cohorts of HCV‐mono‐infected patients. Interestingly, a cluster of SNPs in linkage disequilibrium with rs61183828 is located close to two genes involved in mechanisms affecting both cell signaling and cell structure ( CAV3 ) and HCV replication ( RAD18 ) …”

Section: Disease Progressionmentioning

confidence: 99%

“…Interestingly, a cluster of SNPs in linkage disequilibrium with rs61183828 is located close to two genes involved in mechanisms affecting both cell signaling and cell structure (CAV3) and HCV replication (RAD18). 21…”

Section: Disease Progressionmentioning

confidence: 99%

Host genetic variations associated with disease progression in chronic hepatitis C virus infection

Matsuura

Tanaka

2018

Hepatology Research

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Treatment with recently developed interferon-free oral regimens combining direct-acting antiviral agents (DAAs) results in the elimination of hepatitis C virus (HCV) in almost all chronic hepatitis C (CHC) patients. In the era of DAAs, surveillance of hepatocellular carcinoma (HCC) after eradication of HCV by anti-HCV therapy is particularly important. As is well known, an advanced state of hepatic fibrosis is the major risk factor for developing HCC. Therefore, an increased understanding of various factors associated with disease progression and development of HCC in CHC patients is essential for implementing personalized treatment and surveillance of disease progression and HCC. Recent genome-wide association studies (GWAS) have identified several host genetic variants influencing treatment efficacy or clinical course in HCV infection. This review focuses on these host genetic variations recently identified, mainly by GWAS, which are associated with the clinical course of chronic HCV infection, especially disease progression and hepatocarcinogenesis.

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A new 3p25 locus is associated with liver fibrosis progression in human immunodeficiency virus/hepatitis C virus‐coinfected patients

Cited by 15 publications

References 52 publications

Single-cell analyses reveal aberrant pathways for megakaryocyte-biased hematopoiesis in myelofibrosis and identify mutant clone-specific targets

Single-cell analyses reveal aberrant pathways for megakaryocyte-biased hematopoiesis in myelofibrosis and identify mutant clone-specific targets

Host genetic variation and HIV disease: from mapping to mechanism

Host genetic variations associated with disease progression in chronic hepatitis C virus infection

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