Screening for naturally occurring apolipoprotein A-I variants: apo A-I(ΔK107) is associated with low HDL-cholesterol levels in men but not in women
Screening for naturally occurring apolipoprotein A-I variants: apo A-I(ΔK107) is associated with low HDL-cholesterol levels in men but not in women
复制标题
筛查天然存在的载脂蛋白 A-I 变体：apo A-I (ΔK107) 与男性低 HDL 胆固醇水平相关，但与女性无关
作者：
J. Nofer;A. Eckardstein;H. Wiebusch;W. Weng;H. Funke;H. Schulte;E. Köhler;G. Assmann
平行使用载体两性电解质产生的pH梯度中的等电聚焦（IEF）和非变性条件下固定化pH梯度中的混合等电聚焦（HIEF）来筛选5，500份血浆样本中的载脂蛋白A-I（apo A-I）天然变体。在4例载脂蛋白A-I变体杂合子的无关受试者中发现了以下缺陷：载脂蛋白A-I（ΔK107）（2 ×）、载脂蛋白A-I（K107 M）（1 ×）和载脂蛋白A-I（E41 R）（1 ×）。后一种变体是一个新发现。家族研究未发现载脂蛋白A-I（K107 M）和载脂蛋白A-I（E41 R）与血脂异常有任何关联，但发现了几个载脂蛋白A-I（ΔK107）杂合子，其高密度脂蛋白（HDL）胆固醇水平较低。因此，由于载脂蛋白A-I（ΔK107）是德国最常见的载脂蛋白A-I变异体（1 ∶ 5，000），我们评估了我们的数据和来自11个家庭的32名杂合子携带者和30名未受影响的对照的报告。该分析显示，与未受影响的家族成员以及前瞻性心血管明斯特（PROCAM）研究的对照组相比，apo A-I（ΔK107）与男性HDL-胆固醇降低（-30%）和甘油三酯升高（+48%）相关，但与女性无关。此外，在PROCAM研究中，15例男性apo AI（ΔK107）杂合子中有11例HDL-胆固醇水平低于性别匹配对照的第20百分位数，而17例女性apo AI（ΔK107）杂合子中仅有2例HDL-胆固醇水平低于性别匹配对照的第20百分位数。我们得出结论，apo A-I（ΔK107）杂合性降低HDL-胆固醇，增加甘油三酯在男性中，但不是在女性中。
Isoelectric focussing (IEF) in carrier ampholyte-generated pH gradients and hybrid isoelectric focussing (HIEF) in immobilized pH gradients under nondenaturing conditions were used in parallel to screen 5,500 plasma samples for naturally occurring variants of apolipoprotein A-I (apo A-I). The following defects were identified in four unrelated subjects heterozygous for apo A-I variants: apo A-I(ΔK107)(2 ×), apo A-I(K107M)(1 ×), and apo A-I(E41R)(1 ×). The later variant is a novel finding. Family studies did not reveal any association of apo A-I(K107M) and apo A-I(E41R) with dyslipidemia, but identified several heterozygotes for apo A-I(ΔK107) who had low levels of high density lipoprotein (HDL)cholesterol. Therefore, and since the apo A-I(ΔK107) is the most frequent apo A-I variant in Germany (1 ∶ 5,000) we evaluated our data and that reported from 11 families with 32 heterozygous carriers and 30 unaffected controls. This analysis revealed that apo A-I(ΔK107) is associated with lower HDL-cholesterol (-30%) and higher triglycerides (+ 48%) in men but not in women as compared with unaffected family members as well as with controls from the Prospective Cardiovascular Münster (PROCAM) study. Moreover, 11 of 15 male apo AI(ΔK107) heterozygotes but only 2 of 17 female apo AI(ΔK107) heterozygotes had HDL-cholesterol levels below the 20th percentile of sex-matched controls from the PROCAM study. We conclude that heterozygosity for apo A-I(ΔK107) decreases HDL-cholesterol and increases triglycerides in men but not in women.
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