Umans-Eckenhausen M A, Defesche J C, Sijbrands E J, Scheerder R L, Kastelein J J
Foundation for the Identification of Persons with Inherited Hypercholesterolaemia, Amsterdam, The Netherlands.
Lancet. 2001 Jan 20;357(9251):165-8. doi: 10.1016/S0140-6736(00)03587-X.
Familial hypercholesterolaemia is a common lipid disorder that predisposes for premature cardiovascular disease (CVD). We set up a screening programme in the Netherlands in 1994 to: establish the feasibility of active family screening supported by DNA diagnostics; assess whether or not active identification of these patients with familial hypercholesterolaemia would lead to more cholesterol-lowering treatment; and compare diagnosis by DNA analysis with that by cholesterol measurement.
Both DNA analysis and measurement of cholesterol concentrations were used to screen families in which a functional mutation in the LDL-receptor gene had been detected.
In the first 5 years, 5442 relatives of 237 people with familial hypercholesterolaemia were screened; 2039 individuals were identified as heterozygous by LDL-receptor gene mutation analysis. At the time of examination, 667 of these adults with familial hypercholesterolaemia (39%) received some form of lipid-lowering treatment; 1 year later, this percentage had increased to 93%. In addition, laboratory analysis showed that for carriers as well as non-carriers 18% would have been misdiagnosed by cholesterol measurement alone, with sex-specific and age-specific 90th percentiles of the general Dutch population as diagnostic criteria.
Targeted family screening with DNA analysis proved to be highly effective in identifying patients with hypercholesterolaemia. Most of the identified patients sought treatment and were successfully started on cholesterol-lowering treatment to lower the risk of premature CVD. Our findings could have wider relevance for the screening of other prevalent genetic disorders in the population at large.
家族性高胆固醇血症是一种常见的脂质紊乱疾病，易引发早发性心血管疾病（CVD）。1994年我们在荷兰开展了一项筛查计划，目的是：确定在DNA诊断支持下进行主动家族筛查的可行性；评估主动识别这些家族性高胆固醇血症患者是否会带来更多的降胆固醇治疗；并比较DNA分析诊断与胆固醇测量诊断。
采用DNA分析和胆固醇浓度测量对检测到低密度脂蛋白受体基因突变的家族进行筛查。
在最初的5年里，对237名家族性高胆固醇血症患者的5442名亲属进行了筛查；通过低密度脂蛋白受体基因突变分析，确定了2039人为杂合子。在检查时，这些成年家族性高胆固醇血症患者中有667人（39%）接受了某种形式的降脂治疗；1年后，这一比例增至93%。此外，实验室分析表明，仅以荷兰普通人群的性别和年龄特异性第90百分位数为诊断标准，仅通过胆固醇测量，18%的携带者和非携带者会被误诊。
事实证明，采用DNA分析进行有针对性的家族筛查在识别高胆固醇血症患者方面非常有效。大多数被识别出的患者寻求治疗，并成功开始接受降胆固醇治疗以降低早发性心血管疾病的风险。我们的研究结果可能对更广泛地筛查普通人群中的其他常见遗传疾病具有重要意义。
