Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U980, Paris, France.
Eur J Hum Genet. 2012 Jun;20(6):690-5. doi: 10.1038/ejhg.2011.260. Epub 2012 Jan 18.
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.
人类疱疹病毒 8 型（HHV-8）感染是卡波西肉瘤的病因，已显示出在 HHV-8 感染流行的国家中具有强烈的家族聚集性。我们调查了生活在喀麦隆一个孤立地区的 40 个大家庭（608 名年龄在 1 至 88 岁的受试者），该地区 HHV-8 高度流行。我们对 HHV-8 感染状态（通过免疫荧光法确定的 HHV-8+/HHV-8-）进行了两步遗传分析，包括初始分离分析和基于模型的全基因组连锁分析。总体 HHV-8 血清阳性率为 60%，随年龄增长而增加。分离分析为 HHV-8 感染的隐性主基因赋予易感性提供了强有力的证据。该基因预计在儿童时期具有主要作用，几乎所有纯合易感的受试者（约占人口的 7%）在 10 岁之前就被感染。连锁分析在 15 个最具信息量的家庭中进行，这些家庭对应于 205 个基因分型的受试者。3p22 染色体上的一个单一区域与 HHV-8 感染显著相关（LOD 评分=3.83，P=2.0×10(-5)）。这项研究首次提供了证据，表明流行地区儿童中的 HHV-8 感染具有强烈的遗传基础，涉及至少一个位于 3p22 染色体上的隐性主要基因座。
