ASSOCIATION BETWEEN A SPECIFIC APOLIPOPROTEIN-B MUTATION AND FAMILIAL DEFECTIVE APOLIPOPROTEIN-B-100
ASSOCIATION BETWEEN A SPECIFIC APOLIPOPROTEIN-B MUTATION AND FAMILIAL DEFECTIVE APOLIPOPROTEIN-B-100
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DOI：
10.1073/pnas.86.2.587
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发表时间：
1989-01-01
影响因子：
11.1
通讯作者：
MCCARTHY, BJ
中科院分区：
文献类型：
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作者：
SORIA, LF;LUDWIG, EH;MCCARTHY, BJ
家族性载脂蛋白（apo）B - 100缺陷是一种遗传性疾病，可导致高胆固醇血症以及与载脂蛋白B、E（低密度脂蛋白）受体结合缺陷的低密度脂蛋白血清浓度升高。这种疾病似乎是由apoB - 100基因的突变引起的。对一名该疾病杂合子患者的两个等位基因进行的广泛序列分析显示，在编码氨基酸3500的密码子中存在一种此前未报道的突变，导致精氨酸被谷氨酰胺替代。在其他6名无亲缘关系的患者以及其中两个家族的8名患病亲属中也出现了相同的突变等位基因。通过在已知载脂蛋白B - 100存在变异的位置进行序列分析和限制性内切酶消化，构建了这种突变的apoB - 100等位基因的部分单倍型。在一个家族的3名先证者和4名患病成员中，这种单倍型是相同的，并且缺少一个多态性的Xba I位点，该位点的存在与高胆固醇水平相关。因此，似乎编码氨基酸3500的密码子中的突变（CGG→CAG，一个CG突变“热点”）定义了一种与缺陷型低密度脂蛋白和高胆固醇血症相关的载脂蛋白B - 100次要等位基因。
Familial defective apolipoprotein (apo) B-100 is a genetic disease that leads to hypercholesterolemia and to an increased serum concentration of low density lipoproteins that bind defectively to the apoB, E(LDL) receptor. The disorder appears to result from a mutation in the gene for apoB-100. Extensive sequence analysis of the two alleles of one subject heterozygous for the disorder has revealed a previously unreported mutation in the codon for amino acid 3500 that results in the substitution of glutamine for arginine. This same mutant allele occurs in six other, unrelated subjects and in eight affected relatives in two of these families. A partial haplotype of this mutant apoB-100 allele was constructed by sequence analysis and restriction enzyme digestion at positions where variations in the apoB-100 are known to occur. This haplotype is the same in three probands and four affected members of one family and lacks a polymorphic Xba I site whose presence has been correlated with high cholesterol levels. Thus, it appears that the mutation in the codon for amino acid 3500 (CGG .fwdarw. CAG), a CG mutational "hot spot," defines a minor apoB-100 allele associated with defective low density lipoproteins and hypercholesterolemia.