Genetic Counselor, Center for Inherited Heart Disease, Johns Hopkins University, Baltimore, MD, USA.
Professor, Genomic Medicine Institute, Geisinger, Danville, PA, USA.
J Clin Lipidol. 2020 Jul-Aug;14(4):398-413. doi: 10.1016/j.jacl.2020.04.011. Epub 2020 May 7.
The genetic basis for more than 2 dozen monogenic dyslipidemias has largely been defined. Genetic technologies, such as DNA sequencing, can detect both rare and common DNA variants underlying dyslipidemias, and these methods are increasingly available. Although patients with extreme abnormalities in low-density lipoprotein cholesterol, triglycerides, or high-density lipoprotein cholesterol may be considered for genetic testing, it is only in a minority of patients that the results will alter treatment or outcomes. Currently, there is potential clinical utility of genetic testing for familial hypercholesterolemia, familial chylomicronemia syndrome, sitosterolemia, lysosomal acid lipase deficiency, and a few other rare disorders, and this will increase the demand for reliable genetic diagnostic methods at lower cost. Clinical indications for genetic testing for most dyslipidemias are not clearly established and currently no guidelines exist. A shared decision-making model between the patient and the provider is essential as patient values and preferences play a very strong role. Potential benefits of genetic testing include providing a firm diagnosis in many cases, guiding optimal management and prevention strategies, advancing care strategies beyond currently available treatments, and contributing to overall scientific progress. Understanding the limitations and risks of genetic testing techniques is also important, as is careful interpretation of genetic test results to achieve the greatest benefit. Here we review laboratory methods, as well as technical, biological, clinical, and ethical implications and applications of genetic testing in dyslipidemias.
多种单基因血脂异常的遗传学基础已基本确定。遗传技术，如 DNA 测序，可以检测血脂异常相关的罕见和常见 DNA 变异，并且这些方法的应用越来越广泛。虽然患有极低密度脂蛋白胆固醇、甘油三酯或高密度脂蛋白胆固醇严重异常的患者可能会考虑进行基因检测，但检测结果能改变治疗或预后的情况仅占少数。目前，基因检测对于家族性高胆固醇血症、家族性乳糜微粒血症综合征、植物固醇血症、溶酶体酸性脂肪酶缺乏症和其他一些罕见疾病具有潜在的临床应用价值，这将增加对成本更低的可靠遗传诊断方法的需求。大多数血脂异常基因检测的临床指征尚未明确，目前也没有相关指南。患者和医生之间的共同决策模型至关重要，因为患者的价值观和偏好起着非常重要的作用。基因检测的潜在益处包括在许多情况下提供明确的诊断，指导最佳的管理和预防策略，超越现有治疗方法推进护理策略，并为整体科学进步做出贡献。了解基因检测技术的局限性和风险也很重要，仔细解释基因检测结果以获得最大的收益也很重要。本文综述了血脂异常遗传检测的实验室方法以及技术、生物学、临床和伦理方面的影响和应用。
