The Genetic and Molecular Pathogenesis of Primary Biliary Cirrhosis

原发性胆汁性肝硬化（PBC）是一种慢性肝病，在英国每5000人中就有1人患病。它通常影响中年或老年妇女。没有有效的治疗方法，许多患者最终发展为肝硬化和肝功能衰竭，唯一的治疗方法是肝移植。PBC的病因尚不清楚。然而，有证据表明遗传因素很重要。例如，PBC可能影响同一家庭的不止一个成员。这被称为家族性PBC。导致PBC的基因尚未被明确识别。我们打算研究有几个亲属患有这种疾病的家庭的DNA。我们还将研究一只实验室老鼠，它会患上一种与PBC非常相似的肝脏疾病。通过对PBC家族和PBC小鼠进行基因研究，我们希望能够确定导致该疾病的基因。然后，我们将研究大量非家族性（散发性）PBC患者的DNA，看看是否有相同的基因参与引起散发性疾病。这很重要，因为如果我们确定了导致PBC的基因，研究人员将有更好的机会找到有效的治疗方法。

Primary biliary cirrhosis (PBC) is a chronic liver disease that affects over 1 in 5000 people in the UK. It usually affects middle-aged or older women. There is no effective treatment and many patients eventually develop cirrhosis and liver failure, for which the only treatment is liver transplantation. The cause of PBC is unknown. However, there is evidence that genetic factors are important. For example, PBC may affect more than one member of the same family. This is called familial PBC. The genes involved in causing PBC have not been clearly identified. We intend to study DNA from families in which several relatives have the disease. We will also study a laboratory mouse which develops a liver disease closely resembling PBC. By doing genetic studies of PBC families and the PBC mouse, we hope to identify genes involved in causing the disease. We will then study DNA from a large number of patients with non-familial (sporadic) PBC, to see whether the same genes are involved in causing sporadic disease. This is important because, if we identify the genes involved in causing PBC, investigators will have a better chance of finding a treatment which works.