Apolipoprotein A-I(Zavalla) (Leu159-->Pro): HDL cholesterol deficiency in a kindred associated with premature coronary artery disease.
Apolipoprotein A-I(Zavalla) (Leu159-->Pro): HDL cholesterol deficiency in a kindred associated with premature coronary artery disease.
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载脂蛋白 A-I(Zavalla) (Leu159-->Pro)：HDL 胆固醇缺乏与早发冠状动脉疾病相关。
DOI：
10.1161/01.atv.18.8.1242
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Zeller,K
中科院分区：
文献类型：
--
作者：
Miller,M;Aiello,D;Pritchard,H;Friel,G;Zeller,K
- 我们调查了一位男性先证者及其家庭成员中引起高密度脂蛋白胆固醇（HDL-C）缺乏的分子缺陷。基因组DNA扩增和测序结果显示，载脂蛋白A-I基因第159位残基发生了一个新的碱基对替换。这种取代导致AviII限制性位点的丢失，并且预测第159位残基处的亮氨酸被脯氨酸取代。限制性内切酶分析表明，在40个生物学家族成员中有19个缺乏AviII位点。与家族性对照组相比，apoA-IZavallavariant受试者的HDL-C（1.16 vs 0.27 mmol/L，P<0.0001）、apoA-I（38.7 vs 124.4 mg/dL，P<0.0001）和apoA-II（14.3 vs 19.0 mg/dL，P<0.0001）水平降低。迄今为止发生冠状动脉疾病的两名受试者具有额外的心血管风险因素。其他apoA-IZavalla杂合子目前没有症状性冠状动脉疾病。这项研究确定了一个单基因的原因，低HDL-C表型的单碱基对取代具有主导作用的低HDL-C血症。此外，它扩展了最近的观察结果，即HDL-C缺乏状态可能更容易发生早发性冠状动脉疾病，同时伴有其他心血管危险因素。
—We investigated the molecular defect causing high density lipoprotein cholesterol (HDL-C) deficiency in a male proband and his family members. Amplification and sequencing of genomic DNA disclosed a novel base-pair substitution at residue 159 in the apolipoprotein (apo) A-I gene. This substitution resulted in the loss of anAviII restriction site and a predicted substitution of leucine with proline at residue 159. Restriction enzyme analysis demonstrated absence of theAviII site in 19 of 40 biological family members. Compared with familial controls, subjects with the apoA-IZavallavariant had reduced HDL-C (1.16 versus 0.27 mmol/L,P<0.0001), apoA-I (38.7 versus 124.4 mg/dL,P<0.0001), and apoA-II (14.3 versus 19.0 mg/dL,P<0.0001) levels. Two subjects who have developed coronary artery disease to date possess additional cardiovascular risk factors. Other heterozygotes for apoA-IZavallaare presently without symptomatic coronary artery disease. This study identifies a monogenic cause of hypoalphalipoproteinemia, with the single base-pair substitution having a dominant effect on the low HDL-C phenotype. In addition, it extends recent observations that HDL-C deficiency states may be more prone to the development of premature coronary artery disease when accompanied by additional cardiovascular risk factors.