title: Common polymorphic effectors of immunity against hepatitis B and C modulate susceptibility to infection and spontaneous clearance in a Moroccan population.
abstract: Chronic diseases caused by hepatitis B and C viruses may evolve towards major complications as liver cirrhosis and cancer. Fortunately, only subsets among acutely infected individuals develop a persistent disease suggesting that genetic susceptibility may influence the establishment of chronicity. In the present study we aim to explore variants distribution in genes encoding for important immune response effectors in chronic hepatitis B and C. We intend to identify common features and to establish connections between single nucleotide polymorphisms (SNPs) predisposing to both chronic hepatitis and spontaneous clearance in a Moroccan population. Ten SNPs mapping on seven candidate genes (CD209, TGFβ-1, CCR5, CCL2, CXCL12, SUMO1 and UBC9) were studied in 544 Moroccan subjects grouped in chronically infected patients, spontaneously resolved individuals, liver disease progressors and healthy controls. Among significant associations found between virus infections and genetic variants, we report for the first time an association of rs4804803 (CD209) A and G variants with susceptibility to HBV infection and spontaneous clearance (p<0.001, OR=3.53, 95% CI 2.155; 5.908, and p<0.001, OR=7.75, 95% CI 4.646-13.114, respectively). Other important, albeit previously unknown, association was found between SUMO1 rs10185956T variant and spontaneous clearance of HCV infection (p=0.002, OR=2.71, 95% CI 1.332-5.869). Our observation, that deserves further confirmation with other SNPs and populations, underlines the involvement of selected immune polymorphisms, among which those in CD209, in the natural history of both chronic hepatitis B and C.
authors.affiliation: Virology Unit, Viral Hepatitis Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco.
authors.forename: Khadija
authors.initials: K
authors.lastname: Rebbani
authors.affiliation: Virology Unit, Viral Hepatitis Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco.
authors.forename: Sayeh
authors.initials: S
authors.lastname: Ezzikouri
authors.affiliation: Unité « Organisation nucléaire et oncogenèse », INSERM U993, Institut Pasteur, Paris, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Marchio
authors.affiliation: Virology Unit, Viral Hepatitis Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Ababou
authors.affiliation: Virology Unit, Viral Hepatitis Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco.
authors.forename: Bouchra
authors.initials: B
authors.lastname: Kitab
authors.affiliation: Unité « Organisation nucléaire et oncogenèse », INSERM U993, Institut Pasteur, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Dejean
authors.affiliation: Anthropogenetics and Biotechnolgies Laboratory, School of Science, Chouaïb Doukkali University, El Jadida, Morocco.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Kandil
authors.affiliation: Unité « Organisation nucléaire et oncogenèse », INSERM U993, Institut Pasteur, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Pineau
authors.affiliation: Virology Unit, Viral Hepatitis Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco. Electronic address: soumaya.benjelloun@pasteur.ma.
authors.forename: Soumaya
authors.initials: S
authors.lastname: Benjelloun
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D015815:Cell Adhesion Molecules / Q000235:genetics; D018925:Chemokines / Q000235:genetics; D016000:Cluster Analysis; D018450:Disease Progression; D004198:Disease Susceptibility; D004843:Epistasis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D005787:Gene Frequency; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics; D006509:Hepatitis B / Q000150:complications / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics; D006526:Hepatitis C / Q000150:complications / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D007109:Immunity; D037181:Lectins, C-Type / Q000235:genetics; D008103:Liver Cirrhosis / Q000209:etiology; D008113:Liver Neoplasms / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009018:Morocco; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics; D012703:Serotyping; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D019562:Viral Load; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D018925:Chemokines; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D053773:Transforming Growth Factor beta1; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
keywords: Genetic; Hepatitis; Polymorphism; Spontaneous clearance; Susceptibility