Endokrinologie und Stoffwechsel, Medizinische Klinik III, Zentrum für Innere Medizin, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Atherosclerosis. 2011 Dec;219(2):715-20. doi: 10.1016/j.atherosclerosis.2011.09.030. Epub 2011 Sep 24.
Genomewide association studies (GWAS), conventional association studies and the characterization of families with ApoA5 deficiency have shown that variation in the apolipoprotein A5 (APOA5) gene is associated with plasma triglyceride levels. The aim of this study was to determine the frequency of rare variants in the APOA5 gene in patients with various forms of hypertriglyceridemia.
The DNA sequence of the exons plus exon/intron boundaries of the APOA5 gene of 291 patients with triglycerides above the 95th percentile for age and sex (98 of whom had triglycerides above 875 mg/dl), 111 patients with APOE2/2 genotype of whom 100 had Type III Hyperlipidemia and 108 probands with triglycerides below the 25th percentile for age and sex was determined.
Twenty four variants were detected of which eight have been previously reported. There were nine patients with triglycerides above 875 mg/dl and nine patients with moderately elevated triglycerides who were carriers of at least one deleterious mutation in the APOA5 gene. Of the patients with Type III HLP, three (3%) were carriers of rare variants and there was a single rare variant detected in the group of probands with triglycerides below the 25th percentile for age and sex.
Rare mutations in the APOA5 gene are more frequent in patients with elevated triglycerides than in those with Type III HLP.
全基因组关联研究（GWAS）、传统关联研究以及载脂蛋白 A5（APOA5）基因缺陷家族的特征表明，APOA5 基因的变异与血浆甘油三酯水平有关。本研究旨在确定不同类型高甘油三酯血症患者中 APOA5 基因罕见变异的频率。
测定了 291 名甘油三酯超过年龄和性别第 95 百分位数的患者（其中 98 名甘油三酯超过 875mg/dl）、111 名 APOE2/2 基因型的患者（其中 100 名患有 III 型高脂血症）和 108 名甘油三酯低于年龄和性别第 25 百分位数的患者的 APOA5 基因外显子加外显子/内含子边界的 DNA 序列。
共检测到 24 种变异，其中 8 种已被报道过。有 24 名患者甘油三酯超过 875mg/dl，9 名患者甘油三酯中度升高，他们均携带 APOA5 基因至少一种有害突变。在 III 型 HLP 患者中，有 3 名（3%）携带罕见变异，在甘油三酯低于年龄和性别第 25 百分位数的患者组中检测到 1 种罕见变异。
与 III 型 HLP 患者相比，高甘油三酯血症患者中 APOA5 基因的罕见突变更为常见。
