title: A new 3p25 locus is associated with liver fibrosis progression in human immunodeficiency virus/hepatitis C virus-coinfected patients.
abstract: There is growing evidence that human genetic variants contribute to liver fibrosis in subjects with hepatitis C virus (HCV) monoinfection, but this aspect has been little investigated in patients coinfected with HCV and human immunodeficiency virus (HIV). We performed the first genome-wide association study of liver fibrosis progression in patients coinfected with HCV and HIV, using the well-characterized French National Agency for Research on AIDS and Viral Hepatitis CO13 HEPAVIH cohort. Liver fibrosis was assessed by elastography (FibroScan), providing a quantitative fibrosis score. After quality control, a genome-wide association study was conducted on 289 Caucasian patients, for a total of 8,426,597 genotyped (Illumina Omni2.5 BeadChip) or reliably imputed single-nucleotide polymorphisms. Single-nucleotide polymorphisms with P values <10-6were investigated in two independent replication cohorts of European patients infected with HCV alone. Two signals of genome-wide significance (P < 5 × 10-8) were obtained. The first, on chromosome 3p25 and corresponding to rs61183828 (P = 3.8 × 10-9), was replicated in the two independent cohorts of patients with HCV monoinfection. The cluster of single-nucleotide polymorphisms in linkage disequilibrium with rs61183828 was located close to two genes involved in mechanisms affecting both cell signaling and cell structure (CAV3) or HCV replication (RAD18). The second signal, obtained with rs11790131 (P = 9.3 × 10-9) on chromosome region 9p22, was not replicated.
  
  
  
  This genome-wide association study identified a new locus associated with liver fibrosis severity in patients with HIV/HCV coinfection, on chromosome 3p25, a finding that was replicated in patients with HCV monoinfection; these results provide new relevant hypotheses for the pathogenesis of liver fibrosis in patients with HIV/HCV coinfection that may help define new targets for drug development or new prognostic tests, to improve patient care. (Hepatology 2016;64:1462-1472).
authors.affiliation: Équipe Génomique, Bioinformatique et Applications (EA4627), Chaire de Bioinformatique, Conservatoire National des Arts et Métiers, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Ulveling
authors.affiliation: Équipe Génomique, Bioinformatique et Applications (EA4627), Chaire de Bioinformatique, Conservatoire National des Arts et Métiers, Paris, France.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Le Clerc
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.|Paris Descartes University, Imagine Institute, Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cobat
authors.affiliation: Équipe Génomique, Bioinformatique et Applications (EA4627), Chaire de Bioinformatique, Conservatoire National des Arts et Métiers, Paris, France.
authors.forename: Taoufik
authors.initials: T
authors.lastname: Labib
authors.affiliation: Équipe Génomique, Bioinformatique et Applications (EA4627), Chaire de Bioinformatique, Conservatoire National des Arts et Métiers, Paris, France.
authors.forename: Josselin
authors.initials: J
authors.lastname: Noirel
authors.affiliation: Équipe Génomique, Bioinformatique et Applications (EA4627), Chaire de Bioinformatique, Conservatoire National des Arts et Métiers, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Laville
authors.affiliation: Équipe Génomique, Bioinformatique et Applications (EA4627), Chaire de Bioinformatique, Conservatoire National des Arts et Métiers, Paris, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Coulonges
authors.affiliation: Plateforme Post-Génomique P3S, AP-HP, UPMC Université Paris 6, Faculté de Médecine Pitié Salpétrière, Paris, France.
authors.forename: Wassila
authors.initials: W
authors.lastname: Carpentier
authors.affiliation: Département d'Hépatologie, Hôpital Cochin (AP-HP), Université Paris Descartes, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Nalpas
authors.affiliation: Department of Gastroenterology, University Hospital, Basel, Switzerland.
authors.forename: Markus H
authors.initials: MH
authors.lastname: Heim
authors.affiliation: Université Pierre et Marie Curie, Service d'Hépato-gastroentérologie, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Poynard
authors.affiliation: Epatocentro Ticino, Lugano, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Cerny
authors.affiliation: Département d'Hépatologie, Hôpital Cochin (AP-HP), Université Paris Descartes, Paris, France.|INSERM UMS20, Institut Pasteur, Paris, France.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.affiliation: Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Bochud
authors.affiliation: Centre de Recherche INSERM U897, Epidemiologie-Biostatistique, Institut de Santé Publique, Epidémiologie et Développement, Université de Bordeaux, Bordeaux, France.
authors.forename: François
authors.initials: F
authors.lastname: Dabis
authors.affiliation: Laboratory of Immunity and Infection, Centre d'Immunologie et des Maladies Infectieuses de Paris (CIMI), INSERM U1135, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France.|Plateforme Génomique INSERM-ANRS, Groupe Hospitalier Pitié Salpétrière, AP-HP, UPMC Université Paris 6, Paris, France.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Theodorou
authors.affiliation: INSERM U955, AP-HP, Groupe Henri-Mondor Albert-Chenevier, Immunologie Clinique, Créteil, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Lévy
authors.affiliation: Department of Infectious Diseases, Cochin Hospital, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Salmon
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.|Paris Descartes University, Imagine Institute, Paris, France.|St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.affiliation: INSERM U955, AP-HP, Groupe Henri-Mondor Albert-Chenevier, Immunologie Clinique, Créteil, France. stephanie.dominguez@hmn.aphp.fr.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Dominguez
authors.affiliation: Équipe Génomique, Bioinformatique et Applications (EA4627), Chaire de Bioinformatique, Conservatoire National des Arts et Métiers, Paris, France. zagury@cnam.fr.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Zagury
mesh_terms: D060085:Coinfection; D018450:Disease Progression; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D015658:HIV Infections / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics* / Q000821:virology*; D020641:Polymorphism, Single Nucleotide