A major locus on chromosome 3p22 conferring predisposition to human herpesvirus 8 infection

• Published in: European journal of human genetics : EJHG Vol. 20; no. 6; pp. 690 - 695
• Main Authors: Pedergnana, Vincent, Gessain, Antoine, Tortevoye, Patricia, Byun, Minji, Bacq-Daian, Delphine, Boland, Anne, Casanova, Jean-Laurent, Abel, Laurent, Plancoulaine, Sabine
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.06.2012
• Subjects: Adolescent; Adult; Age; Aged; Aged, 80 and over; Antibodies, Viral; Antibodies, Viral - immunology; Biological and medical sciences; Cameroon; Chemokines; Child; Child, Preschool; Children; Chromosome 3; Chromosomes; Chromosomes, Human, Pair 3; Chromosomes, Human, Pair 3 - genetics; Cytokines; Dermatology; Families & family life; Family; Female; Fundamental and applied biological sciences. Psychology; Genes; Genes, Recessive; Genetic analysis; Genetic Predisposition to Disease; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genomes; Herpes simplex; Herpesviridae Infections; Herpesviridae Infections - genetics; Herpesviridae Infections - transmission; Herpesviridae Infections - virology; Herpesvirus 8, Human; Herpesvirus 8, Human - immunology; Herpesvirus 8, Human - pathogenicity; Human herpesvirus 8; Humans; Immunofluorescence; Infant; Infection; Infections; Infectious diseases; Kaposi's sarcoma; Life Sciences; Linkage analysis; Male; Medical genetics; Medical sciences; Middle Aged; Molecular and cellular biology; Population; Proteins; Sarcoma; Seroepidemiologic Studies; Studies; Tuberculosis; Tumors of the skin and soft tissue. Premalignant lesions; Viruses; Cameroon; France; Skin disease; Pathogenesis; Genetic determinism; Kaposi sarcoma; Human herpesvirus 8; Predisposition; Genetics; Population; Locus; endemic population; Gammaherpesvirinae; Genetic mapping; Human; Herpesviridae; Kaposi's sarcoma-associated herpes virus; Herpes; Chromosome; Malignant tumor; Virus; Infection; Associated virus; Segregation analysis; linkage analysis; Viral disease; Genetic linkage; Inheritance(genetics); Severe; Cancer
• ISSN: 1018-4813; 1476-5438; 1476-5438
• DOI: 10.1038/ejhg.2011.260

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.