Apolipoprotein B-gene DNA polymorphisms associated with myocardial infarction.

Levels of apolipoprotein B, the protein component of low-density lipoproteins, correlate with the risk of coronary heart disease. We examined whether genetic variation in apolipoprotein B is associated with myocardial infarction by studying apolipoprotein B-gene restriction-fragment-length polymorphisms in 84 patients with myocardial infarction and an equal number of matched controls. Southern blot analysis with apolipoprotein B-gene probes, performed after DNA was digested with the endonucleases XbaI and EcoRI, revealed alleles that we designated as X1, X2, and X3 and as R1 and R2, respectively. Similar studies with the endonuclease MspI revealed alleles of many different sizes (the difference was due to an insertion-deletion polymorphism), which we grouped as larger and smaller alleles and designated as ID1 and ID2, respectively. The frequencies of the X1, R1, and ID1 alleles were all significantly higher (P less than 0.01) in the cases than in the controls. None of the alleles, however, was significantly associated with variation in levels of low-density lipoprotein cholesterol or apolipoprotein B, and the functional importance of these alleles is therefore uncertain. Nonetheless, in addition to quantitative variation in apolipoprotein B levels in plasma, genetic variation at the apolipoprotein B locus may be a new and independent risk factor for myocardial infarction.

[1]  P. Wilson,et al.  Apolipoprotein A-I gene polymorphism associated with premature coronary artery disease and familial hypoalphalipoproteinemia. , 1986, The New England journal of medicine.

[2]  S. Young,et al.  Parallel expression of the MB19 genetic polymorphism in apoprotein B-100 and apoprotein B-48. Evidence that both apoproteins are products of the same gene. , 1986, The Journal of biological chemistry.

[3]  C. Ehnholm,et al.  Apolipoprotein E polymorphism in the Finnish population: gene frequencies and relation to lipoprotein concentrations. , 1986, Journal of lipid research.

[4]  R. Ross.  The pathogenesis of atherosclerosis--an update. , 1986, The New England journal of medicine.

[5]  D. Miller,et al.  Mapping of the human APOB gene to chromosome 2p and demonstration of a two-allele restriction fragment length polymorphism. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[6]  S. Young,et al.  Monoclonal antibody MB19 detects genetic polymorphism in human apolipoprotein B. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[7]  P. Carlsson,et al.  Molecular cloning of human apolipoprotein B cDNA. , 1985, Nucleic acids research.

[8]  A. Camm,et al.  DNA polymorphisms in the apolipoprotein C-III and insulin genes and atherosclerosis. , 1985, Atherosclerosis.

[9]  S. Naylor,et al.  Human apolipoprotein B-100: cloning, analysis of liver mRNA, and assignment of the gene to chromosome 2. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[10]  D. Ledbetter,et al.  The human apolipoprotein B-100 gene: a highly polymorphic gene that maps to the short arm of chromosome 2. , 1985, Biochemical and biophysical research communications.

[11]  V. Schumaker,et al.  Human apolipoprotein B: identification of cDNA clones and characterization of mRNA. , 1985, Nucleic acids research.

[12]  R. Eddy,et al.  Human apolipoprotein B: structure of carboxyl-terminal domains, sites of gene expression, and chromosomal localization. , 1985, Science.

[13]  A. Kessling,et al.  A study of DNA polymorphisms around the human apolipoprotein Al gene in hyperlipidaemic and normal individuals , 1985, Clinical genetics.

[14]  S. Karathanasis.  Apolipoprotein multigene family: tandem organization of human apolipoprotein AI, CIII, and AIV genes. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[15]  J. Breslow,et al.  Human apolipoprotein B cDNA clone isolation and demonstration that liver apolipoprotein B mRNA is 22 kilobases in length. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[16]  J. Scott,et al.  RFLP for the human apolipoprotein B gene: I;BamHI. , 1985, Nucleic acids research.

[17]  C. Shoulders,et al.  Deoxyribonucleic acid polymorphism in the apolipoprotein A-1-C-III gene cluster. Association with hypertriglyceridemia. , 1985, The Journal of clinical investigation.

[18]  D. Galton,et al.  GENETIC POLYMORPHISMS OF APOLIPOPROTEIN C-III AND INSULIN IN SURVIVORS OF MYOCARDIAL INFARCTION , 1985, The Lancet.

[19]  A. Motulsky,et al.  A partial cDNA clone for human apolipoprotein B. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[20]  J. Hyams,et al.  Apolipoprotein B-100 deficiency. Intestinal steatosis despite apolipoprotein B-48 synthesis. , 1985, The Journal of clinical investigation.

[21]  M. Brown,et al.  How LDL receptors influence cholesterol and atherosclerosis. , 1984, Scientific American.

[22]  C. Shoulders,et al.  DNA POLYMORPHISM ADJACENT TO HUMAN APOPROTEIN A-1 GENE: RELATION TO HYPERTRIGLYCERIDAEMIA , 1983, The Lancet.

[23]  K. Berg.  Genetics of coronary heart disease. , 1983, Progress in medical genetics.

[24]  J. Breslow,et al.  Linkage of human apolipoproteins A-I and C-III genes , 1983, Nature.

[25]  A. Tall,et al.  Role of apolipoprotein E-containing lipoproteins in abetalipoproteinemia. , 1982, The Journal of clinical investigation.

[26]  J. Albers,et al.  Dextran sulfate-Mg2+ precipitation procedure for quantitation of high-density-lipoprotein cholesterol. , 1982, Clinical chemistry.

[27]  T. Musliner,et al.  Radioimmunoassay of Apolipoprotein A‐II , 1982, Arteriosclerosis.

[28]  C. Blum,et al.  Radioimmunoassay studies of human apolipoprotein E. , 1980, The Journal of clinical investigation.

[29]  J. Kane,et al.  Heterogeneity of apolipoprotein B: isolation of a new species from human chylomicrons. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[30]  D. Botstein,et al.  Construction of a genetic linkage map in man using restriction fragment length polymorphisms. , 1980, American journal of human genetics.

[31]  A. Shaw.  Letter: Another blood product. , 1974, Lancet.

[32]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.