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.
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Acknowledgements
We thank the families from the Ntem valley for their participation in this study; Alain Froment, Philippe Tuppin, Edouard Betsem and Richard Njouom for assistance with data collection; and all members of the two branches of the Laboratory of Human Genetics of Infectious Diseases for fruitful discussions. This work was supported by INSERM, Institut Pasteur and Centre National de Génotypage, Centre National de la Recherche Scientifique (CNRS, Comité Environnement et Santé), Association pour la Recherche contre le Cancer (ARC), Programme National de Recherche Fondamentale en Microbiologie et Maladies Infectieuses et Parasitaires, Institut Pasteur (action concertée Inter-Pasteurienne for ‘HHV-8 and Kaposi's Sarcoma in intertropical countries’), the Rockefeller University Center for Clinical and Translational Science grant number 5UL1RR024143, The Rockefeller University and St Giles Foundation. SP received funding from Assistance-Publique–Hôpitaux de Paris. MB was supported by the Irvington Institute Fellowship Program of the Cancer Research Institute.
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Pedergnana, V., Gessain, A., Tortevoye, P. et al. A major locus on chromosome 3p22 conferring predisposition to human herpesvirus 8 infection. Eur J Hum Genet 20, 690–695 (2012). https://doi.org/10.1038/ejhg.2011.260
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DOI: https://doi.org/10.1038/ejhg.2011.260
