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Hepatology. 2016 Nov;64(5):1462-1472. doi: 10.1002/hep.28695. Epub 2016 Jul 29.

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

Author information

1
Équipe Génomique, Bioinformatique et Applications (EA4627), Chaire de Bioinformatique, Conservatoire National des Arts et Métiers, Paris, France.
2
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.
3
Paris Descartes University, Imagine Institute, Paris, France.
4
Plateforme Post-Génomique P3S, AP-HP, UPMC Université Paris 6, Faculté de Médecine Pitié Salpétrière, Paris, France.
5
Département d'Hépatologie, Hôpital Cochin (AP-HP), Université Paris Descartes, Paris, France.
6
Department of Gastroenterology, University Hospital, Basel, Switzerland.
7
Université Pierre et Marie Curie, Service d'Hépato-gastroentérologie, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France.
8
Epatocentro Ticino, Lugano, Switzerland.
9
INSERM UMS20, Institut Pasteur, Paris, France.
10
Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland.
11
Centre de Recherche INSERM U897, Epidemiologie-Biostatistique, Institut de Santé Publique, Epidémiologie et Développement, Université de Bordeaux, Bordeaux, France.
12
Laboratory of Immunity and Infection, Centre d'Immunologie et des Maladies Infectieuses de Paris (CIMI), INSERM U1135, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France.
13
Plateforme Génomique INSERM-ANRS, Groupe Hospitalier Pitié Salpétrière, AP-HP, UPMC Université Paris 6, Paris, France.
14
INSERM U955, AP-HP, Groupe Henri-Mondor Albert-Chenevier, Immunologie Clinique, Créteil, France.
15
Department of Infectious Diseases, Cochin Hospital, Paris, France.
16
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
17
INSERM U955, AP-HP, Groupe Henri-Mondor Albert-Chenevier, Immunologie Clinique, Créteil, France. stephanie.dominguez@hmn.aphp.fr.
18
Équipe Génomique, Bioinformatique et Applications (EA4627), Chaire de Bioinformatique, Conservatoire National des Arts et Métiers, Paris, France. zagury@cnam.fr.

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 <10-6 were 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.

CONCLUSION:

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).

PMID:
27339598
DOI:
10.1002/hep.28695
[Indexed for MEDLINE]

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