title: A major locus on chromosome 3p22 conferring predisposition to human herpesvirus 8 infection.
abstract: Infection with human herpesvirus 8 (HHV-8), the etiological agent of Kaposi's sarcoma, has been shown to display strong familial aggregation, in countries in which HHV-8 infection is endemic. We investigated 40 large families (608 subjects aged one to 88 years) living in an isolated area of Cameroon in which HHV-8 is highly endemic. We performed a two-step genetic analysis for HHV-8 infection status (HHV-8+/HHV-8- determined by immunofluorescence) consisting of an initial segregation analysis followed by a model-based genome-wide linkage analysis. Overall HHV-8 seroprevalence was 60%, increasing with age. Segregation analysis provided strong evidence for a recessive major gene conferring predisposition to HHV-8 infection. This gene is predicted to have a major effect during childhood, with almost all homozygous predisposed subjects (∼7% of the population) becoming infected by the age of 10. Linkage analysis was carried out on the 15 most informative families, corresponding to 205 genotyped subjects. A single region on chromosome 3p22 was significantly linked to HHV-8 infection (LOD score=3.83, P=2.0 × 10(-5)). This study provides the first evidence that HHV-8 infection in children in endemic areas has a strong genetic basis involving at least one recessive major locus on chromosome 3p22.
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U980, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Pedergnana
authors.forename: Antoine
authors.initials: A
authors.lastname: Gessain
authors.forename: Patricia
authors.initials: P
authors.lastname: Tortevoye
authors.forename: Minji
authors.initials: M
authors.lastname: Byun
authors.forename: Delphine
authors.initials: D
authors.lastname: Bacq-Daian
authors.forename: Anne
authors.initials: A
authors.lastname: Boland
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Sabine
authors.initials: S
authors.lastname: Plancoulaine
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000276:immunology; D002163:Cameroon; D002648:Child; D002675:Child, Preschool; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005190:Family; D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006566:Herpesviridae Infections / Q000235:genetics* / Q000635:transmission / Q000821:virology*; D019288:Herpesvirus 8, Human / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D016036:Seroepidemiologic Studies
chemical_list: D000914:Antibodies, Viral