期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1992
卷号：89
期号：2
页码：708-712
DOI：10.1073/pnas.89.2.708
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
