Endokrinologikum Frankfurt, Stresemannallee 3, 60596 Frankfurt, Germany.
Eur J Med Res. 2011 Feb 24;16(2):79-84. doi: 10.1186/2047-783x-16-2-79.
Type III Hyperlipoproteinemia is a rare lipid disorder with a frequency of 1-5 in 5000. It is characterized by the accumulation of triglyceride rich lipoproteins and patients are at increased risk of developping atherosclerosis. Type III HLP is strongly associated with the homozygous presence of the ε2 allele of the APOE gene. However only about 10% of subjects with APOE2/2 genotype develop hyperlipidemia and it is therefore assumed that further genetic and environmental factors are necessary for the expression of disease. It has recently been shown that variation in the APOA5 gene is one of these co-factors. The aim of this study is to investigate the development of cerebrovascular athero?sclerosis in patients with Type III hyperlipopro?teinemia (Type III HLP) and the role of variation in the APOA5 gene as a risk factor.
60 patients with type III hyperlipidemia and ApoE2/2 genotype were included in the study after informed consent. The presence of cerebrovascular atherosclerosis was investigated using B-mode ultrasonography of the carotid artery. Serum lipid levels were measured by standard procedures.The APOE genotype and the 1131T>C and S19W SNPs in the APOA5 gene and the APOC3 sstI SNP were determined by restriction isotyping. Allele frequencies were determined by gene counting and compared using Fisher's exact test. Continuous variables were compared using the Mann Whitney test. A p value of 0.05 or below was considered statistically significant. Analysis was performed using Statistica 7 software.
The incidence of the APOA5 SNPs, -1131T>C and S19W and the APOC3 sstI SNP were determined as a potential risk modifier. After correction for conventional risk factors, the C allele of the -1131T>C SNP in the APOA5 gene was associated with an increased risk for the development of carotid plaque in patients with Type III HLP with an odds ratio of 3.69. Evaluation of the genotype distribution was compatible with an independent effect of APOA5.
The development of atherosclerosis in patients with Type III HLP is modulated by variation in the APOA5 gene.
III 型高脂蛋白血症是一种罕见的脂质疾病，发病率为每 5000 人中 1-5 例。其特征是富含甘油三酯的脂蛋白积累，患者发生动脉粥样硬化的风险增加。III 型 HLP 与 APOE 基因的 ε2 等位基因的纯合存在强烈相关。然而，只有约 10%的 APOE2/2 基因型的受试者发生高脂血症，因此认为还需要进一步的遗传和环境因素来表达疾病。最近已经表明，APOA5 基因的变异是这些共同因素之一。本研究的目的是研究 III 型高脂蛋白血症（III 型 HLP）患者的脑血管动脉粥样硬化的发展，以及 APOA5 基因变异作为危险因素的作用。
在获得知情同意后，本研究纳入了 60 例 III 型高脂血症和 ApoE2/2 基因型的患者。使用颈动脉 B 型超声检查评估脑血管动脉粥样硬化的存在。血清脂质水平通过标准程序进行测量。APOE 基因型和 APOA5 基因的 1131T>C 和 S19W SNPs 以及 APOC3 sstI SNP 通过限制酶切分型确定。等位基因频率通过基因计数确定，并使用 Fisher 精确检验进行比较。连续变量使用 Mann-Whitney 检验进行比较。p 值<0.05 被认为具有统计学意义。分析使用 Statistica 7 软件进行。
确定了 APOA5 基因的-1131T>C 和 S19W 以及 APOC3 sstI SNP 的等位基因频率，作为潜在的风险修饰因子。在对传统危险因素进行校正后，APOA5 基因的-1131T>C SNP 的 C 等位基因与 III 型 HLP 患者颈动脉斑块形成的风险增加相关，优势比为 3.69。基因型分布的评估与 APOA5 的独立作用一致。
III 型 HLP 患者的动脉粥样硬化发展受 APOA5 基因变异的调节。
