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.
Hum Genet. 2009 Nov;126(5):697-705. doi: 10.1007/s00439-009-0721-y. Epub 2009 Jul 23.
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.
丙型肝炎病毒（HCV）感染全球 1.7 亿人，是一个主要的公共卫生问题。在发展中国家，不安全的注射和输血被认为是主要的传播途径。然而，我们之前在埃及的一个丙型肝炎流行人群中的研究显示，存在显著的家族相关性，强烈提示病毒的家族传播和对 HCV 感染的遗传易感性的存在。我们通过在同一人群中对 HCV 感染进行分离分析，研究了遗传易感性的假设。我们使用逻辑回归模型，同时考虑主要基因效应、家族相关性和相关危险因素。我们分析了 312 个家系（3703 名受试者）。总的 HCV 血清阳性率为 11.8%，并随年龄增长而增加。主要相关危险因素是以前针对血吸虫病的肠外治疗和输血。我们发现了强有力的证据表明显性主要基因赋予了 HCV 感染易感性。易感等位基因的频率为 0.013，反映了 2.6%的受试者，特别是 20 岁以下的受试者，对 HCV 感染有强烈的易感性。这项研究为宿主遗传因素在地方性感染条件下对 HCV 感染的易感性/抗性的参与提供了证据。
