Gardemann A, Ohly D, Fink M, Katz N, Tillmanns H, Hehrlein F W, Haberbosch W
Institut für Klinische Chemie und Pathobiochemie, Klinikum der Justus-Liebig-Universität Giessen, Germany.
Atherosclerosis. 1998 Nov;141(1):167-75. doi: 10.1016/s0021-9150(98)00161-0.
The Del allele of the apolipoprotein B (apoB) signal peptide (SP) insertion/deletion (Ins/Del) polymorphism has been shown to be associated with elevated plasma levels of apoB, cholesterol and low density lipoprotein. It was the aim of the present study to analyse the relation of this gene variation to the risk of coronary artery disease (CAD) and of myocardial infarction (MI) in a population of 2259 male Caucasians, whose coronary anatomy was defined by means of coronary angiography. ApoB SP DelDel genotypes had significantly higher apoB plasma concentrations than InsIns homozygotes (P = 0.0001) and InsDel heterozygotes (P = 0.002); however, the apoB plasma levels of InsIns and InsDel genotypes were essentially the same (P = 0.54). Similar observations were made with respect to ApoB SP genotype-dependent cholesterol plasma concentrations. Since the apoB plasma level was not only associated with the apoB SP Ins/Del gene variation but also to the extent of coronary artery disease (P <0.0001), individuals with an InsIns genotype and without CAD had the lowest and subjects with a DelDel genotype and triple vessel disease the highest apoB plasma levels (P <0.0001). An association of the apoB SP Ins/Del gene variation with CAD was not detected, neither in the total population nor in low risk groups. In contrast, the gene variation was associated with MI (P <0.05). An Odds ratio of 1.18 (95% CI, 1.01-1.39) associated with the Del allele was detected in the total sample (P <0.02). In a subpopulation of individuals with low plasma triglyceride levels ( <154 mg/dl; mean value) and an DD genotype of the angiotensin I-converting enzyme insertion/deletion gene polymorphism an Odds ratio of 2.01 (1.42-3.05) was calculated (P <0.001). The present study presents evidence for a statistically significant difference in the development of MI between genotype classes of the apoB SP Ins/Del gene polymorphism.
载脂蛋白B（apoB）信号肽（SP）插入/缺失（Ins/Del）多态性的Del等位基因已被证明与血浆中apoB、胆固醇和低密度脂蛋白水平升高有关。本研究的目的是分析在2259名男性白种人组成的人群中，这种基因变异与冠状动脉疾病（CAD）和心肌梗死（MI）风险之间的关系，这些人的冠状动脉解剖结构通过冠状动脉造影来确定。ApoB SP DelDel基因型的血浆apoB浓度显著高于InsIns纯合子（P = 0.0001）和InsDel杂合子（P = 0.002）；然而，InsIns和InsDel基因型的血浆apoB水平基本相同（P = 0.54）。关于ApoB SP基因型依赖性血浆胆固醇浓度也有类似的观察结果。由于血浆apoB水平不仅与apoB SP Ins/Del基因变异有关，还与冠状动脉疾病的程度有关（P <0.0001），InsIns基因型且无CAD的个体血浆apoB水平最低，而DelDel基因型且有三支血管病变的个体血浆apoB水平最高（P <0.0001）。在总体人群或低风险组中均未检测到apoB SP Ins/Del基因变异与CAD之间的关联。相比之下，该基因变异与MI有关（P <0.05）。在总样本中检测到与Del等位基因相关的比值比为1.18（95%可信区间，1.01 - 1.39）（P <0.02）。在血浆甘油三酯水平较低（<154 mg/dl；平均值）且血管紧张素I转换酶插入/缺失基因多态性为DD基因型的亚组人群中，计算出比值比为2.01（1.42 - 3.05）（P <0.001）。本研究提供了证据，表明apoB SP Ins/Del基因多态性的基因型类别在MI发生方面存在统计学上的显著差异。
