Clinic for Special Children, Strasburg, PA, USA.
Center for Special Children - La Farge Medical Clinic - Vernon Memorial Healthcare, La Farge, WI, USA.
BMC Cardiovasc Disord. 2022 Mar 17;22(1):109. doi: 10.1186/s12872-022-02539-3.
Familial hypercholesterolemia (FH) due to a founder variant in Apolipoprotein B (ApoB) is reported in 12% of the Pennsylvania Amish community. By studying a cohort of ApoB heterozygotes and homozygotes, we aimed to characterize the biochemical and cardiac imaging features in children and young adults with a common genetic background and similar lifestyle.
We employed advanced lipid profile testing, carotid intima media thickness (CIMT), pulse wave velocity (PWV), and peripheral artery tonometry (PAT) to assess atherosclerosis in a cohort of Amish ApoB heterozygotes (n = 13), homozygotes (n = 3), and their unaffected, age-matched siblings (n = 9). ApoB homozygotes were not included in statistical comparisons.
LDL cholesterol (LDL-C) was significantly elevated among ApoB heterozygotes compared to sibling controls, though several ApoB heterozygotes had LDL-C levels in the normal range. LDL particles (LDL-P), small, dense LDL particles, and ApoB were also significantly elevated among subjects with ApoB. Despite these differences in serum lipids and particles, CIMT and PWV were not significantly different between ApoB heterozygotes and controls in age-adjusted analysis.
We provide a detailed description of the serum lipids, atherosclerotic plaque burden, vascular stiffness, and endothelial function among children and young adults with FH due to heterozygous ApoB. Fasting LDL-C was lower than what is seen with other forms of FH, and even normal in several ApoB heterozygotes, emphasizing the importance of cascade genetic testing among related individuals for diagnosis. We found increased number of LDL particles among ApoB heterozygotes but an absence of detectable atherosclerosis.
在宾夕法尼亚州的阿米什社区，12%的家族性高胆固醇血症（FH）归因于载脂蛋白 B（ApoB）的创始人变体。通过研究载脂蛋白 B 杂合子和纯合子的队列，我们旨在描述具有共同遗传背景和相似生活方式的儿童和年轻成人的生化和心脏成像特征。
我们采用先进的血脂谱检测、颈动脉内膜中层厚度（CIMT）、脉搏波速度（PWV）和外周动脉张力计（PAT）评估一组阿米什载脂蛋白 B 杂合子（n=13）、纯合子（n=3）及其无影响、年龄匹配的兄弟姐妹（n=9）的动脉粥样硬化情况。载脂蛋白 B 纯合子不包括在统计比较中。
与兄弟姐妹对照组相比，载脂蛋白 B 杂合子的 LDL 胆固醇（LDL-C）显著升高，尽管一些载脂蛋白 B 杂合子的 LDL-C 水平在正常范围内。载脂蛋白 B 患者的 LDL 颗粒（LDL-P）、小而密的 LDL 颗粒和载脂蛋白 B 也明显升高。尽管血清脂质和颗粒存在这些差异，但在年龄调整分析中，载脂蛋白 B 杂合子与对照组之间的 CIMT 和 PWV 无显著差异。
我们详细描述了杂合子载脂蛋白 B 导致的 FH 儿童和年轻成人的血清脂质、动脉粥样硬化斑块负担、血管僵硬和内皮功能。空腹 LDL-C 低于其他形式的 FH，甚至在几个载脂蛋白 B 杂合子中也正常，强调了对相关个体进行级联基因检测以进行诊断的重要性。我们发现载脂蛋白 B 杂合子中的 LDL 颗粒数量增加，但未检测到可察觉的动脉粥样硬化。
