Linkage of atherogenic lipoprotein phenotype to the low density lipoprotein receptor locus on the short arm of chromosome 19.
Linkage of atherogenic lipoprotein phenotype to the low density lipoprotein receptor locus on the short arm of chromosome 19.
复制标题
致动脉粥样硬化脂蛋白表型与 19 号染色体短臂上的低密度脂蛋白受体基因座的关联。
DOI：
10.1073/pnas.89.2.708
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发表时间：
1992
影响因子：
11.1
通讯作者：
Krauss,RM
中科院分区：
文献类型：
--
作者：
Nishina,PM;Johnson,JP;Naggert,JK;Krauss,RM
致动脉粥样硬化性脂蛋白表型(ALP)是一种常见的可遗传特征，其特征是以细小致密的低密度脂蛋白(B亚型)颗粒为主，富含甘油三酯的脂蛋白水平增加，高密度脂蛋白降低，心肌梗死风险增加3倍。在9个B型ALP先证者的51个家系中，发现ALP与19号染色体短臂上的低密度脂蛋白受体基因座存在显著的两点连锁。假设ALP B型外显率为100%，重组分数为0.04时的最大优势对数(LOD)为4.07，假设B型外显率为90%，则为4.27。单倍型数据和多点连锁分析表明，ALP的致病基因[命名为动脉粥样硬化易感性(脂蛋白相关)ATHS]位于D19S76的远端，靠近或位于低密度脂蛋白受体基因座上。这一结果提示，在普通人群中，低密度脂蛋白受体基因座或19号染色体上紧密连锁的基因座上的遗传变异可能是导致B型ALP代谢改变的原因，这种代谢改变在普通人群中占相当大比例的家族性冠状动脉疾病易感性。
The atherogenic lipoprotein phenotype (ALP) is a common heritable trait characterized by a predominance of small, dense low density lipoprotein (LDL) particles (subclass pattern B), increased levels of triglyceride-rich lipoproteins, reductions in high density lipoprotein, and a 3-fold increased risk of myocardial infarction. Significant two-point linkage was found between ALP and the LDL receptor locus on the short arm of chromosome 19 in 51 relatives of nine probands with ALP pattern B. The maximum logarithm of odds (LOD) score of 4.07 was observed at a recombination fraction of 0.04, assuming 100% penetrance of ALP pattern B, and 4.27 at a recombination fraction of zero, assuming 90% penetrance of pattern B. Haplotyping data and multipoint linkage analysis suggest that the gene [named ATHS for atherosclerosis susceptibility (lipoprotein-associated)] responsible for ALP is located distal to D19S76 near or at the LDL receptor locus. This result suggests the possibility that genetic variation at the LDL receptor locus or a closely linked locus on chromosome 19 may be responsible for metabolic alterations in ALP pattern B that account for a substantial proportion of the familial predisposition to coronary artery disease in the general population.
DOI：
--
发表时间：
1972
期刊：
影响因子：
--
作者：
G. Nelson
通讯作者：
G. Nelson
连锁和基因顺序委员会的报告。
DOI：
--
发表时间：
1988
期刊：
Cytogenetics and Cell Genetics
影响因子：
--
作者：
B. Keats;J. Ott;P. Conneally
通讯作者：
P. Conneally