Benes Lane B, Brummell Kent, Roth Mendel, Shen Li, Davidson Michael H
The University of Chicago Medicine, Section of Cardiology, 5841 S Maryland Avenue, MC 6080, Chicago, IL 60637, USA.
The University of Chicago Department of Internal Medicine, 5841 S Maryland Avenue, Chicago, IL 60637, USA.
Cardiovasc Revasc Med. 2020 Feb;21(2):200-204. doi: 10.1016/j.carrev.2019.04.006. Epub 2019 May 8.
Genetic information is not routinely obtained in the management of most lipid disorders or in primary or secondary prevention of cardiovascular disease (CVD). We sought to determine the prevalence of pathogenic variants associated with lipoprotein metabolism or coronary artery disease (CAD) in a single lipid clinic and discuss the future use of genetic information in CVD prevention.
Genetic testing was offered to patients with hypertriglyceridemia (defined as pre-treatment fasting triglycerides ≥150 mg/dL), elevated LDL-C (defined as pre-treatment ≥190 mg/dL), low HDL-C (defined as ≤40 mg/dL), elevated lipoprotein (a) (defined as ≥50 mg/dL or 100 nmol/L) or premature CAD (defined as an acute coronary syndrome or revascularization before age 40 years in men and 50 years in women) using next-generation DNA sequencing of 327 exons and selected variants in 129 genes known or suspected to be associated with lipoprotein metabolism or CAD.
82 of 84 patients (97.6%) were found to have a variant associated with abnormal lipid metabolism or CAD. The most common pathogenic or likely pathogenic variants included those of the LDL receptor (15 patients) and lipoprotein lipase (9 patients). Other common variants included those of apolipoprotein A5 (14 patients) and variants associated with elevated lipoprotein (a) (25 patients).
The majority of patients presenting to a single lipid clinic were found to have at least one variant associated with abnormal lipoprotein metabolism or CAD. Incorporating genetic information, including the use of genetic risk scores, is anticipated in the future care of lipid disorders and CVD prevention.
在大多数血脂异常的管理或心血管疾病（CVD）的一级或二级预防中，通常不会获取遗传信息。我们试图确定在一家血脂诊所中与脂蛋白代谢或冠状动脉疾病（CAD）相关的致病变异的患病率，并讨论遗传信息在CVD预防中的未来应用。
对患有高甘油三酯血症（定义为治疗前空腹甘油三酯≥150mg/dL）、低密度脂蛋白胆固醇升高（定义为治疗前≥190mg/dL）、高密度脂蛋白胆固醇降低（定义为≤40mg/dL）、脂蛋白（a）升高（定义为≥50mg/dL或100nmol/L）或早发CAD（定义为男性在40岁之前、女性在50岁之前发生急性冠状动脉综合征或血运重建）的患者，使用下一代DNA测序技术对327个外显子和129个已知或怀疑与脂蛋白代谢或CAD相关的基因中的选定变异进行检测。
84例患者中有82例（97.6%）被发现存在与脂质代谢异常或CAD相关的变异。最常见的致病或可能致病变异包括低密度脂蛋白受体变异（15例患者）和脂蛋白脂肪酶变异（9例患者）。其他常见变异包括载脂蛋白A5变异（14例患者）和与脂蛋白（a）升高相关的变异（25例患者）。
在一家血脂诊所就诊的大多数患者被发现至少有一种与脂蛋白代谢异常或CAD相关的变异。预计在未来血脂异常的治疗和CVD预防中会纳入遗传信息，包括使用遗传风险评分。
