title: Evidence for a dominant major gene conferring predisposition to hepatitis C virus infection in endemic conditions.
abstract: Hepatitis C virus (HCV), infecting 170 million people worldwide, is a major public health problem. In developing countries, unsafe injections and blood transfusions are thought to be the major routes of transmission. However, our previous work in a population from Egypt, endemic for HCV, revealed highly significant familial correlations, strongly suggesting the existence of both familial transmission of the virus and genetic predisposition to HCV infection. We investigated the hypothesis of genetic predisposition by carrying out a segregation analysis of HCV infection in the same population. We used a logistic regression model simultaneously taking into account a major gene effect, familial correlations and relevant risk factors. We analyzed 312 pedigrees (3,703 subjects). Overall HCV seroprevalence was 11.8% and increased with age. The main associated risk factors were previous parenteral treatment for schistosomiasis and blood transfusions. We found strong evidence for a dominant major gene conferring a predisposition to HCV infection. The frequency of the predisposing allele was 0.013, reflecting a strong predisposition to HCV infection in 2.6% of the subjects, particularly those under the age of 20. This study provides evidence for the involvement of host genetic factors in susceptibility/resistance to HCV infection in endemic conditions.
authors.affiliation: Laboratoire de Génétique Humaine des Maladies Infectieuses, Faculté de Médecine Necker, Institut National de la Santé et de la Recherche Médicale (INSERM), U550, 75015 Paris, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Laouénan
authors.forename: Sabine
authors.initials: S
authors.lastname: Plancoulaine
authors.forename: Mostafa Kamal
authors.initials: MK
authors.lastname: Mohamed
authors.forename: Naglaa
authors.initials: N
authors.lastname: Arafa
authors.forename: Iman
authors.initials: I
authors.lastname: Bakr
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdel-Hamid
authors.forename: Claire
authors.initials: C
authors.lastname: Rekacewicz
authors.forename: Dorothée
authors.initials: D
authors.lastname: Obach
authors.forename: Arnaud
authors.initials: A
authors.lastname: Fontanet
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
mesh_terms: D000328:Adult; D000367:Age Factors; D000375:Aging; D002648:Child; D004534:Egypt / Q000453:epidemiology; D019353:Endemic Diseases / Q000706:statistics & numerical data*; D005190:Family; D005260:Female; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006526:Hepatitis C / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011336:Probability; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D012727:Sex Characteristics; D035781:Siblings; D055815:Young Adult