Association of the insertion/deletion gene polymorphism of the apolipoprotein B signal peptide with myocardial infarction.

The Del allele of the apolipoprotein B (apoB) signal peptide (SP) insertion/deletion (Ins/Del) polymorphism has been shown to be associated with elevated plasma levels of apoB, cholesterol and low density lipoprotein. It was the aim of the present study to analyse the relation of this gene variation to the risk of coronary artery disease (CAD) and of myocardial infarction (MI) in a population of 2259 male Caucasians, whose coronary anatomy was defined by means of coronary angiography. ApoB SP DelDel genotypes had significantly higher apoB plasma concentrations than InsIns homozygotes (P = 0.0001) and InsDel heterozygotes (P = 0.002); however, the apoB plasma levels of InsIns and InsDel genotypes were essentially the same (P = 0.54). Similar observations were made with respect to ApoB SP genotype-dependent cholesterol plasma concentrations. Since the apoB plasma level was not only associated with the apoB SP Ins/Del gene variation but also to the extent of coronary artery disease (P <0.0001), individuals with an InsIns genotype and without CAD had the lowest and subjects with a DelDel genotype and triple vessel disease the highest apoB plasma levels (P <0.0001). An association of the apoB SP Ins/Del gene variation with CAD was not detected, neither in the total population nor in low risk groups. In contrast, the gene variation was associated with MI (P <0.05). An Odds ratio of 1.18 (95% CI, 1.01-1.39) associated with the Del allele was detected in the total sample (P <0.02). In a subpopulation of individuals with low plasma triglyceride levels ( <154 mg/dl; mean value) and an DD genotype of the angiotensin I-converting enzyme insertion/deletion gene polymorphism an Odds ratio of 2.01 (1.42-3.05) was calculated (P <0.001). The present study presents evidence for a statistically significant difference in the development of MI between genotype classes of the apoB SP Ins/Del gene polymorphism.

[1]  A. Gardemann,et al.  Gene polymorphism but not catalytic activity of angiotensin I-converting enzyme is associated with coronary artery disease and myocardial infarction in low-risk patients. , 1995, Circulation.

[2]  R. Ward,et al.  Apolipoprotein Polymorphisms Fail to Define Risk of Coronary Artery Disease: Results of a Prospective, Angiographically Controlled Study , 1994, Circulation.

[3]  L. Prencipe,et al.  Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. , 1982, Clinical chemistry.

[4]  Philippe Amouyel,et al.  Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction , 1992, Nature.

[5]  E. Boerwinkle,et al.  Signal Peptide–Length Variation in Human Apolipoprotein B Gene: Molecular Characteristics and Association with Plasma Glucose Levels , 1991, Diabetes.

[6]  P. Talmud,et al.  DNA polymorphisms of the apoprotein B gene are associated with altered plasma lipoprotein concentrations but not with perceived risk of cardiovascular disease: European Atherosclerosis Research Study. , 1995, Atherosclerosis.

[7]  S. D. Mohamed,et al.  Abnormal histidine metabolism in thyrotoxicosis in man. A possible index of impaired folate function. , 1965, Lancet.

[8]  R Kreutz,et al.  A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease. , 1995, The New England journal of medicine.

[9]  F. Cambien,et al.  Relation of parental history of early myocardial infarction to the level of apoprotein B in men. , 1987, Circulation.

[10]  S. Jeffery,et al.  Angiotensin-converting enzyme gene polymorphism. What to do about all the confusion. , 1996, Circulation.

[11]  K. Gould,et al.  Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial , 1990, The Lancet.

[12]  R. Brasseur,et al.  Human apolipoprotein B signal sequence variants confer a secretion-defective phenotype when expressed in yeast. , 1993, The Journal of biological chemistry.

[13]  P Corvol,et al.  An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. , 1990, The Journal of clinical investigation.

[14]  T. Sørensen,et al.  ACE gene polymorphism: ischemic heart disease and longevity in 10,150 individuals. A case-referent and retrospective cohort study based on the Copenhagen City Heart Study. , 1997, Circulation.

[15]  S. Lowe,et al.  Defective receptor binding of low density lipoprotein from pigs possessing mutant apolipoprotein B alleles. , 1988, The Journal of biological chemistry.

[16]  L. Kuller,et al.  SERUM CHOLESTEROL, BLOOD PRESSURE, AND MORTALITY: IMPLICATIONS FROM A COHORT OF 361 662 MEN , 1986, The Lancet.

[17]  A. Clauss,et al.  Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens , 1957 .

[18]  R. Krauss,et al.  Defective catabolism and abnormal composition of low-density lipoproteins from mutant pigs with hypercholesterolemia. , 1988, Biochemistry.

[19]  J. Erikssen,et al.  The apolipoprotein B signal peptide insertion/deletion polymorphism is not associated with myocardial infarction in Norway , 1994, Clinical genetics.

[20]  J. Strong,et al.  Apo B insertion/deletion polymorphisms are associated with atherosclerosis in young black but not young white males. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. , 1992, Arteriosclerosis and thrombosis : a journal of vascular biology.

[21]  Thomas J. White,et al.  PCR protocols: a guide to methods and applications. , 1990 .

[22]  P. Wilson,et al.  Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. , 1986, JAMA.

[23]  A. G. Steinberg,et al.  Progress in Medical Genetics , 1970 .

[24]  S. Hong,et al.  Genetic variation of the apolipoprotein B gene in Korean patients with coronary artery disease. , 1997, Molecules and cells.

[25]  G. Gensini,et al.  A more meaningful scoring system for determining the severity of coronary heart disease. , 1983, The American journal of cardiology.

[26]  N. Yoshiike,et al.  Association of apolipoprotein genetic polymorphisms with plasma cholesterol in a Japanese rural population. The Shibata Study. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[27]  R. Krauss,et al.  Familial defective apolipoprotein B-100: a mutation of apolipoprotein B that causes hypercholesterolemia. , 1990, Journal of lipid research.

[28]  A. Gressner,et al.  Measurement of proteins with the Behring Nephelometer. A multicentre evaluation. , 1989, Journal of clinical chemistry and clinical biochemistry. Zeitschrift fur klinische Chemie und klinische Biochemie.

[29]  A. Attie,et al.  Overproduction of a buoyant low density lipoprotein subspecies in spontaneously hypercholesterolemic mutant pigs. , 1991, Arteriosclerosis and thrombosis : a journal of vascular biology.

[30]  E. Boerwinkle,et al.  A three codon insertion/deletion polymorphism in the signal peptide region of the human apolipoprotein B (APOB) gene directly typed by the polymerase chain reaction. , 1989, Nucleic acids research.

[31]  G. Möller,et al.  Multicentre Study of a New Enzymatic Method of Cholesterol Determination , 1984, Journal of clinical chemistry and clinical biochemistry. Zeitschrift fur klinische Chemie und klinische Biochemie.

[32]  S M Grundy,et al.  Dietary influences on serum lipids and lipoproteins. , 1990, Journal of lipid research.

[33]  P. Talmud,et al.  Apolipoprotein B signal peptide insertion/deletion polymorphism is associated with Ag epitopes and involved in the determination of serum triglyceride levels. , 1990, Journal of lipid research.

[34]  S. Glišić,et al.  Study of apoB gene signal peptide insertion/deletion polymorphism in a healthy Serbian population: no association with serum lipid levels. , 1997, Clinica chimica acta; international journal of clinical chemistry.

[35]  E. Kawasaki.  18 – SAMPLE PREPARATION FROM BLOOD, CELLS, AND OTHER FLUIDS , 1990 .

[36]  S. Grundy,et al.  Overproduction of Low Density Lipoproteins Associated with Coronary Heart Disease , 1983, Arteriosclerosis.

[37]  R. Corbo,et al.  Apolipoproteins B and E, and angiotensin I‐converting enzyme (ACE) genetic polymorphisms in Italian women with coronary artery disease (CAD) and their relationships with plasma lipid and apolipoprotein levels , 1997, Clinical genetics.

[38]  N. Samani,et al.  A meta-analysis of the association of the deletion allele of the angiotensin-converting enzyme gene with myocardial infarction. , 1996, Circulation.

[39]  P. Talmud,et al.  Apolipoprotein B gene polymorphisms, lipoproteins and coronary atherosclerosis: a study of young myocardial infarction survivors and healthy population-based individuals. , 1992, Atherosclerosis.