Faculty Research 1990 - 1999
Linkage of atherogenic lipoprotein phenotype to the low density lipoprotein receptor locus on the short arm of chromosome 19.
Document Type
Article
Publication Date
1992
Keywords
Chromosome-Mapping, Chromosomes-Human-Pair-19, Genetic-Markers, Human, Linkage-(Genetics), Lipoproteins-HDL, Lipoproteins-LDL, Pedigree, Phenotype, Receptors-Insulin: ge, Receptors-LDL: ge, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-NON-P-H-S, SUPPORT-U-S-GOVT-P-H-S
First Page
708
Last Page
712
JAX Source
Proc Natl Acad Sci U S A 1992 Jan 15;89(2):708-12
Grant
HL18574
Abstract
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.
Recommended Citation
Nishina PM,
Johnson JP,
Naggert JK,
Krauss RM.
Linkage of atherogenic lipoprotein phenotype to the low density lipoprotein receptor locus on the short arm of chromosome 19. Proc Natl Acad Sci U S A 1992 Jan 15;89(2):708-12