Epidemiology of Hereditary Haemochromatosis

目前公共卫生面临的挑战之一是将人类基因组计划的进展转化为减少疾病的发病率和死亡率。一旦确定了基因缺陷的特征，从公共卫生的角度来看，了解突变携带者疾病严重程度的可变性是很重要的。遗传性血色沉着症(HH)是一种常见的铁超载遗传性疾病，可导致多种疾病，从非特异性症状到铁沉积对肝脏、心脏、胰腺和关节的严重损害。通过定期献血可以很容易地治疗它，因此主张对HH进行基于人群的筛查。在这项研究中，我们的目标是解决HH现有数据中与饮食和生活方式因素有关的差距，这些因素有助于HH的不同临床图景。这项研究将基于墨尔本合作队列研究，该队列由31,500名男性和女性组成，他们已经被跟踪了大约10年。在最初登记时收集了有关饮食和生活方式因素的信息，以及血液样本。我们将对所有非南欧参与者(31,176人)进行HFE基因常见HH突变的检测，然后选择1150人作为亚组，包括所有有主要基因缺陷的人和对照组，进行进一步的临床随访。参与者将接受遗传咨询，并将获得知情同意。参与者将完成一份简短的问卷，并提供血样进行铁超载、肝功能和其他相关血液检查，然后进行简短的临床检查。所有测试的结果将在遗传顾问或医生的后续访问中给出。这项研究将提供影响临床表现可变性的HH风险因素的自然病史以及HFE突变与慢性病和所有原因死亡的关联的重要数据。

One of the current challenges in public health is to translate the progress from the Human Genome Project into reduced morbidity and mortality from disease. Once genetic defects are characterised, knowledge about the variability in severity of disease in mutation carriers, is important from a public health perspective. Hereditary Haemochromatosis (HH) is a common genetic disorder of iron overload that results in a wide spectrum of disease, varying from non-specific symptoms to severe damage to liver, heart, pancreas and joints from iron deposition. It is easily treatable by regular blood donation, and population-based screening for HH has therefore been advocated. In this study we aim to address gaps in the existing data on HH regarding dietary and lifestyle factors that contribute to the variable clinical picture of HH. The study will be based on the Melbourne Collaborative Cohort Study, a cohort of 31,500 men and women who have been followed for approximately 10 years. Information on dietary and lifestyle factors was collected at initial enrollment, along with a blood specimen. We will test all non-Southern European participants (31,176) for the common HH mutations in the HFE gene and then select a subgroup of 1150 people, including all people with the main genetic defect as well as a comparison group, for further clinical followup. Participants will have genetic counselling and informed consent will be obtained. Participants will complete a short questionnaire and give a blood sample for measurement of iron overload, liver function, and other relevant blood tests, then undergo a brief clinical examination. Results of all tests will be given at a followup visit by genetic counsellor or physician. This study will provide important data on natural history of HH risk factors that influence variability in clinical presentation and the association of HFE mutations with chronic diseases and all cause mortality.