Influence of Apo E Polymorphism on Coronary Artery Disease
The ε4 allele of the ε2, ε3 and ε4 protein isoform polymorphism in the gene encoding apolipoprotein E (Apo E) has previously been associated with increased cardiac artery disease (CAD); therefore to investigate the significance of this polymorphism in pathogenesis of CAD in Iranian patients with stenosis and control subjects. To investigate the association between
Apo E polymorphism and coronary artery disease we performed a comparative case control study of the frequency of Apo E
polymorphism in One hundred CAD patients with stenosis who underwent coronary angiography (>50% stenosis) and 100 control subjects (<10% stenosis). The Apo E alleles and genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). We observed an association between the Apo E polymorphism and CAD in this study. These data suggest that the Apo ε4 and ε2 alleles increase the risk for CAD in Iranian population (χ2 =4.26, p= 0.05, OR=2 and χ2 =0.38, p=0.53, OR=1.2). These results suggest that ε4 and ε2 alleles are risk factors for stenosis.
[1] Mahley RW. Apo lipoprotein E: cholesterol transport protein with
expending role in cell. Science, 1988; 240: 622-630.
[2] Siest G, Pillot T, Regis - Bailly A, Leininger - Muller B, Steinmetz J
and Galteau MM. Apolipoprotein E : An important gene and protein to
follow in laboratory medicine. Clin- Chem 1995; 41: 1068-1086.
[3] Paik YK, Chang DJ, Reardon CA, Davies GE, Mahle RW and Tayler
JM. Nucleotide sequence and structure of the human opolipoprotein E
gene. Procnat, Acad Sci USA 1985; 82: 3445-3449.
[4] Das HK, Mcpherson J, Bruns GA, Karathasis SX and Breslow JL.
Isolation characterization and mapping to chromosome 19 of the human
apolipoprotein E gene. J Biol Chem 1985; 60: 6240-6247.
[5] Smith M, Vonder Kooij- Meijis E, Frants RR, Havekes L and Klasen
EC. Apolipoprotein gene claster on chromosome 19: Defenite
localization of the top C2 gene and the polymorphic Hha 1 site
associated with type 1 hyperlipoproteinemia. Hum Genet. 1988; 78: 90-
93.
[6] Ilveskosk G , Perola N and Lethimalei J. Age dependent association of
opolipoprotein E genotype with coronary and aortic atherosclerosis in
middle -aged men an autopsy study. Circulation 1999; 100: 608-813.
[7] Utermann G, Largen beek U, Beisiegel U and weber W. Genetics of the
apolipoprotein E system in men. Am J Hum Genet, 1982; 32: 339-347.
[8] Breslov Jl . Apolipoprotein genetic variation and human disease. Phsiol.
Rev. 1988; 68: 85-98.
[9] Hallman DM, Boerwinkle E, Sandholzer C , Menzei HJ and Csazar A.
The apolipoprotein E polymorphism; a comparison of allele frequencies
and effects in nine populations . Am J Hum Genet, 1991; 49: 338-349.
[10] Boenwinkle E, Visvikls S, Weisn D, Steinmetz J, Hanash Sm and Sing
Cf. The use of measured genotype information in the analysis of
quantitative phenotypes in man: The role of the apolipoprotein E
polymorphism in determining levels, variability and co- variability of
cholesterol, betalipoprotein and triglycerides in a sample of unrelated
individuals . Am J Med Genet , 1987; 27: 567-582.
[11] Davignon J. Apolipoprotein E polymorphism and atherosclerosis. In.
Born Gvr Schwatz Cy. (Cds). New Horizons in coronary heart disease.
Curr. Sci. 1993; 5: 5.1-5.21.
[12] Genovefa O, Kolovou , Katherimek A and nagnostopoulou . A
polipoprotein E polymorphism age and coronary heart disease. Ageing
Research reviews. 2007; 6: 94-108.
[13] Cord EH, Sauders AM. Gene dose of apolipoprotein E type allele 4 and
the risk of alzimer's disease in late onset families. 1993; 13: 261(5123)
828-829.
[14] Yilman M. Hemostatic markers and renal function after cardiopulmonary
bypass. Asian Cardiovasc Thrac Ann 2001; 9: 86-89.
[15] Miller SA, Dykes DD and Polesky HF. A simple salting out procedure
for extracting DNA from human nucleated cells. Nucleic acid Res 1988;
16: 1215-1218.
[16] Hixson JE and Vernier DT. Restriction isotyping of human
apolipoprotein E by gene amplification and cleavage with Hha 1. J lipid
Res. 1990; 51: 545-548.
[17] Eichner Je, Dunn T, Perveen G, Thompson DM, Stewart RE and
Strochla BC. Apolipoprotein E polymorphism and cardiovascular
disease a huge review. AM J Epidem. 2003; 155: 487-495.
[18] Breslow JC. Apolypoprotein genetic variation and human disease.
Physiol. Rev. 1988,; 68: 85-98.
[19] Ventakaramana P, Chengal RE and Ferrell RE. Apolipoprotein E
polymorphism in two populations of Andru Pradesh. Ind J Hum Genet
2002; 3: 1-5.
[20] Uterman G, Hardewing A and Zimmer F. Apolipoprotein E phenotypes
in patients with myocardial infarction. Hum Genet. 1984; 65: 237-241.
[21] Lehtinens Lehtimalci T, Sisto, Salenius TP, Mikkila M and Jakela H.
Apolipoprotein E polymorphism, serum lipid, myocardial infarction and
severity of angiographically verified coronary datery disease in men and
women . Atheroscelorosis; 1995; 114: 83-91.
[22] Dembinska Kiee A, Kawecka- Jaszez K, Kwasniak M, Gaevaro I,
Pankiewicz J and Maiczewsiea Maleec M. Apo E isoforms , insulin out
put and plasma lipid levels in essential by hypertension . Eur J Clin
Invest, 1998; 28: 95-99.
[23] Yilmas H, Isbir J, Agachan B and Aydin M. Is epsilon 4 allele of
apolipoprotein E associated with more severe end stage in essential
hypertension? Cell Biochem. Funct 2001; 19: 191-195.
[24] Li X, Duy, DUY and Huang X. Association of apolipoprotein E gene
polymorphism with essential hypertension and its complication. Clin
Exp Med. 2003; 2: 175-179.
[25] Couderc R, Mahleumof, Bailleu S, Fencon G, Mary R, Fermahken J.
Prevalence of apolipoprotein E phenotypes in ischemic cerebrovascular
disease. Stroke 1993; 24: 661-664.
[26] Yiaqing S, Meir J, Stampher . Apolipoprotein E Genotypes Coronary
Heart Disease. Annals of Internal Medicine 2004; 141: 137-147.
[27] Bharani AB, Sastry KB, Krishna Reddy N and Padma T. Lipid profile
and apolipoprotein E polymorphism in essential hypertension. Indian
Heart J 2005; 57: 1115-11117.
[28] Hubacok JA, Adamakovu V and Skodova I. Phisol Res. 2005; 54: 573-
582.
[29] Merho Shin, Hce Nsm Kim, Lian- Hua Coul Sun- Song, Kwoon,
Kjaooag- Soopark, Heam-Heo, Churg, Jin-Sn . J Korean Med Sci 2003,
20: 361-366.
[30] Dallongeville J, lussier Caean S and Darignon J. Modulation of plasma
triglyceride levels by apo E phenotype: a meta analysis. J lipid Res.
1992; 33: 447-454.
[31] Simopoulo AP. Genetic variation and nutrition. Word Rev Nutr Diet.
1999; 84: 118-140.
[32] Knijff P, Havefes LM. Apolipoprotein E as a risk factor for coronary
heart disease: a genetic and molecular biology approach Curr Opin Lipid
1996; 7: 59-63.
[33] Luss, W, Bolduc A , Auigness M, Niyonsengu T and Sing CF. Effect of
alcohol in take of lipid metabolism depends on ......... Tmunb Ratc Fial
2002; 22: 1824-1831.
[34] Nucklus BJ, Ferrull Re, Bunjaul LB, Berumun DM and Dennis KE
Gold- bery AP. Effect of apolipoprotein E genotype on dietary- induced
changes in high density lipoprotein cholesterol in obese postmenopause
women. Metabolism 2002; 51: 853-858.
[35] Reznik Y, Merallo R, Poosse P, Mahoudeau J and Fradins. The effect of
age body mass index and fasting triglceride level on postprandial lipemia
is dependet on opolipoprotein E polymorphism in subjects with noninsulin
dependent diabetes. Metabolism 2002; 51: 1088-1092.
[36] Andrade DE, Thandi M, Brown S, Gaho A, Patsch W and Boerwinke E.
Relationship of the apolipoprotein E gene and early carotide
atherosclerosis defined by ultrasonography in asymptomatic adults.
Arterioscler Thromb Vasc Biol 1997; 9: 91-97.
[37] Lusis A, Mar Rand J and Pajakanta P. Genetics of atherosclerosis.
Anna Rev. Genomics Hum. Genet. 2004; 5: 184-218.
[38] Dallongevill J, Lussier-Cacan S and Davignon J. Modulation of plasma
triglyceride levels by apo E phenotype: a meta -analysis. J Lipid Res.
1992; 33: 447-454.
[39] Davignon J, Cohn JS, Mabile L and Bernier L. Apolipoprotein E and
atherosclerosis : insight from animal and human studies. Clin Chim Acta
1999; 286- 115-43.
[40] Davignon J, Gregg RE and Sing CF. Apolipoprotein E polymorphism
and atherosclerosis. Arteriosclerosis 1988; 8: 1-21.
[41] Zerba KE, Ferrell Rm and Sing CF. Genotype-environment interaction:
apolipoprotein E gene effects and gene as an index of time and spatial
context in humans. Genetics 1996; 143: 463-478.
[42] Reilly S, Ferrell R, Kottke B and Sing CF. The gender- specific
apolipoprotein E genotype influence on the distribution of lipids and
apolipoproteins in the population of Rochester, MN. 11. Regression
relationships with concomitants. Am J Hum Genet 1992; 51: 1311-1324.
[43] Reilly S, Ferrell R and Sing CF. The gender -specific apolipoprotein E
genotype influence on the distribution of lipids and apolipoproteins in
the population of Rochester, MN. 111. Correlations and covariances.
Am J Hum Genet 1994; 55: 1001-1018.
[44] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009; 131:
149-50.
[1] Mahley RW. Apo lipoprotein E: cholesterol transport protein with
expending role in cell. Science, 1988; 240: 622-630.
[2] Siest G, Pillot T, Regis - Bailly A, Leininger - Muller B, Steinmetz J
and Galteau MM. Apolipoprotein E : An important gene and protein to
follow in laboratory medicine. Clin- Chem 1995; 41: 1068-1086.
[3] Paik YK, Chang DJ, Reardon CA, Davies GE, Mahle RW and Tayler
JM. Nucleotide sequence and structure of the human opolipoprotein E
gene. Procnat, Acad Sci USA 1985; 82: 3445-3449.
[4] Das HK, Mcpherson J, Bruns GA, Karathasis SX and Breslow JL.
Isolation characterization and mapping to chromosome 19 of the human
apolipoprotein E gene. J Biol Chem 1985; 60: 6240-6247.
[5] Smith M, Vonder Kooij- Meijis E, Frants RR, Havekes L and Klasen
EC. Apolipoprotein gene claster on chromosome 19: Defenite
localization of the top C2 gene and the polymorphic Hha 1 site
associated with type 1 hyperlipoproteinemia. Hum Genet. 1988; 78: 90-
93.
[6] Ilveskosk G , Perola N and Lethimalei J. Age dependent association of
opolipoprotein E genotype with coronary and aortic atherosclerosis in
middle -aged men an autopsy study. Circulation 1999; 100: 608-813.
[7] Utermann G, Largen beek U, Beisiegel U and weber W. Genetics of the
apolipoprotein E system in men. Am J Hum Genet, 1982; 32: 339-347.
[8] Breslov Jl . Apolipoprotein genetic variation and human disease. Phsiol.
Rev. 1988; 68: 85-98.
[9] Hallman DM, Boerwinkle E, Sandholzer C , Menzei HJ and Csazar A.
The apolipoprotein E polymorphism; a comparison of allele frequencies
and effects in nine populations . Am J Hum Genet, 1991; 49: 338-349.
[10] Boenwinkle E, Visvikls S, Weisn D, Steinmetz J, Hanash Sm and Sing
Cf. The use of measured genotype information in the analysis of
quantitative phenotypes in man: The role of the apolipoprotein E
polymorphism in determining levels, variability and co- variability of
cholesterol, betalipoprotein and triglycerides in a sample of unrelated
individuals . Am J Med Genet , 1987; 27: 567-582.
[11] Davignon J. Apolipoprotein E polymorphism and atherosclerosis. In.
Born Gvr Schwatz Cy. (Cds). New Horizons in coronary heart disease.
Curr. Sci. 1993; 5: 5.1-5.21.
[12] Genovefa O, Kolovou , Katherimek A and nagnostopoulou . A
polipoprotein E polymorphism age and coronary heart disease. Ageing
Research reviews. 2007; 6: 94-108.
[13] Cord EH, Sauders AM. Gene dose of apolipoprotein E type allele 4 and
the risk of alzimer's disease in late onset families. 1993; 13: 261(5123)
828-829.
[14] Yilman M. Hemostatic markers and renal function after cardiopulmonary
bypass. Asian Cardiovasc Thrac Ann 2001; 9: 86-89.
[15] Miller SA, Dykes DD and Polesky HF. A simple salting out procedure
for extracting DNA from human nucleated cells. Nucleic acid Res 1988;
16: 1215-1218.
[16] Hixson JE and Vernier DT. Restriction isotyping of human
apolipoprotein E by gene amplification and cleavage with Hha 1. J lipid
Res. 1990; 51: 545-548.
[17] Eichner Je, Dunn T, Perveen G, Thompson DM, Stewart RE and
Strochla BC. Apolipoprotein E polymorphism and cardiovascular
disease a huge review. AM J Epidem. 2003; 155: 487-495.
[18] Breslow JC. Apolypoprotein genetic variation and human disease.
Physiol. Rev. 1988,; 68: 85-98.
[19] Ventakaramana P, Chengal RE and Ferrell RE. Apolipoprotein E
polymorphism in two populations of Andru Pradesh. Ind J Hum Genet
2002; 3: 1-5.
[20] Uterman G, Hardewing A and Zimmer F. Apolipoprotein E phenotypes
in patients with myocardial infarction. Hum Genet. 1984; 65: 237-241.
[21] Lehtinens Lehtimalci T, Sisto, Salenius TP, Mikkila M and Jakela H.
Apolipoprotein E polymorphism, serum lipid, myocardial infarction and
severity of angiographically verified coronary datery disease in men and
women . Atheroscelorosis; 1995; 114: 83-91.
[22] Dembinska Kiee A, Kawecka- Jaszez K, Kwasniak M, Gaevaro I,
Pankiewicz J and Maiczewsiea Maleec M. Apo E isoforms , insulin out
put and plasma lipid levels in essential by hypertension . Eur J Clin
Invest, 1998; 28: 95-99.
[23] Yilmas H, Isbir J, Agachan B and Aydin M. Is epsilon 4 allele of
apolipoprotein E associated with more severe end stage in essential
hypertension? Cell Biochem. Funct 2001; 19: 191-195.
[24] Li X, Duy, DUY and Huang X. Association of apolipoprotein E gene
polymorphism with essential hypertension and its complication. Clin
Exp Med. 2003; 2: 175-179.
[25] Couderc R, Mahleumof, Bailleu S, Fencon G, Mary R, Fermahken J.
Prevalence of apolipoprotein E phenotypes in ischemic cerebrovascular
disease. Stroke 1993; 24: 661-664.
[26] Yiaqing S, Meir J, Stampher . Apolipoprotein E Genotypes Coronary
Heart Disease. Annals of Internal Medicine 2004; 141: 137-147.
[27] Bharani AB, Sastry KB, Krishna Reddy N and Padma T. Lipid profile
and apolipoprotein E polymorphism in essential hypertension. Indian
Heart J 2005; 57: 1115-11117.
[28] Hubacok JA, Adamakovu V and Skodova I. Phisol Res. 2005; 54: 573-
582.
[29] Merho Shin, Hce Nsm Kim, Lian- Hua Coul Sun- Song, Kwoon,
Kjaooag- Soopark, Heam-Heo, Churg, Jin-Sn . J Korean Med Sci 2003,
20: 361-366.
[30] Dallongeville J, lussier Caean S and Darignon J. Modulation of plasma
triglyceride levels by apo E phenotype: a meta analysis. J lipid Res.
1992; 33: 447-454.
[31] Simopoulo AP. Genetic variation and nutrition. Word Rev Nutr Diet.
1999; 84: 118-140.
[32] Knijff P, Havefes LM. Apolipoprotein E as a risk factor for coronary
heart disease: a genetic and molecular biology approach Curr Opin Lipid
1996; 7: 59-63.
[33] Luss, W, Bolduc A , Auigness M, Niyonsengu T and Sing CF. Effect of
alcohol in take of lipid metabolism depends on ......... Tmunb Ratc Fial
2002; 22: 1824-1831.
[34] Nucklus BJ, Ferrull Re, Bunjaul LB, Berumun DM and Dennis KE
Gold- bery AP. Effect of apolipoprotein E genotype on dietary- induced
changes in high density lipoprotein cholesterol in obese postmenopause
women. Metabolism 2002; 51: 853-858.
[35] Reznik Y, Merallo R, Poosse P, Mahoudeau J and Fradins. The effect of
age body mass index and fasting triglceride level on postprandial lipemia
is dependet on opolipoprotein E polymorphism in subjects with noninsulin
dependent diabetes. Metabolism 2002; 51: 1088-1092.
[36] Andrade DE, Thandi M, Brown S, Gaho A, Patsch W and Boerwinke E.
Relationship of the apolipoprotein E gene and early carotide
atherosclerosis defined by ultrasonography in asymptomatic adults.
Arterioscler Thromb Vasc Biol 1997; 9: 91-97.
[37] Lusis A, Mar Rand J and Pajakanta P. Genetics of atherosclerosis.
Anna Rev. Genomics Hum. Genet. 2004; 5: 184-218.
[38] Dallongevill J, Lussier-Cacan S and Davignon J. Modulation of plasma
triglyceride levels by apo E phenotype: a meta -analysis. J Lipid Res.
1992; 33: 447-454.
[39] Davignon J, Cohn JS, Mabile L and Bernier L. Apolipoprotein E and
atherosclerosis : insight from animal and human studies. Clin Chim Acta
1999; 286- 115-43.
[40] Davignon J, Gregg RE and Sing CF. Apolipoprotein E polymorphism
and atherosclerosis. Arteriosclerosis 1988; 8: 1-21.
[41] Zerba KE, Ferrell Rm and Sing CF. Genotype-environment interaction:
apolipoprotein E gene effects and gene as an index of time and spatial
context in humans. Genetics 1996; 143: 463-478.
[42] Reilly S, Ferrell R, Kottke B and Sing CF. The gender- specific
apolipoprotein E genotype influence on the distribution of lipids and
apolipoproteins in the population of Rochester, MN. 11. Regression
relationships with concomitants. Am J Hum Genet 1992; 51: 1311-1324.
[43] Reilly S, Ferrell R and Sing CF. The gender -specific apolipoprotein E
genotype influence on the distribution of lipids and apolipoproteins in
the population of Rochester, MN. 111. Correlations and covariances.
Am J Hum Genet 1994; 55: 1001-1018.
[44] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009; 131:
149-50.
@article{"International Journal of Medical, Medicine and Health Sciences:64085", author = "S. Fallah and M. Seifi and M. Firoozrai and T. Godarzi and M. Jafarzadeh and L. H. Ghohari", title = "Influence of Apo E Polymorphism on Coronary Artery Disease", abstract = "The ε4 allele of the ε2, ε3 and ε4 protein isoform polymorphism in the gene encoding apolipoprotein E (Apo E) has previously been associated with increased cardiac artery disease (CAD); therefore to investigate the significance of this polymorphism in pathogenesis of CAD in Iranian patients with stenosis and control subjects. To investigate the association between
Apo E polymorphism and coronary artery disease we performed a comparative case control study of the frequency of Apo E
polymorphism in One hundred CAD patients with stenosis who underwent coronary angiography (>50% stenosis) and 100 control subjects (", keywords = "Arterial blood vessels, atherosclerosis, cholesterol.", volume = "3", number = "9", pages = "263-5", }
