Genetic polymorphism of the E apolipoprotein in school age children: comparison with levels of plasma lipids and apolipoproteins
Keywords:
polymorphism, genetic, apolipoproteins, cholesterol, triglycerides, child, adolescent
Abstract
Introduction. Research in laboratories around the world has documented the contribution of the E apolipoprotein alleles to structural variations of lipids and apolipoproteins.Objective. The gene frequencies of the E apolipoprotein alleles were compared with the lipid and apolipoprotein levels in school age children.
Materials and methods. Six hundred and ninety one 5 to 15 years old school age children from the Colombian departments of Cundinamarca, Boyacá, Meta, Santander and Norte de Santander, were evaluated.The genotypes of the E apolipoprotein were identified by polymerase chain reaction-restriction fragment length polymorphism. Plasma levels for the following 5 lipids and lipoproteins were assayed: total cholesterol, HDL (high density lipoprotein) cholesterol, LDL (low density lipoprotein) cholesterol, triglycerides, VLDL (very low density lipoprotein) cholesterol, A-I apolipoprotein and B-100 apolipoprotein.
Results. Alleles e2, e3 and e4 were found in frequencies of 0.04, 0.86 and 0.08, respectively. The E4 group (E4/3-E4/4), in contrast with the E2 group (E3/2-E2/2), presented highest plasma concentrations of total cholesterol, LDL cholesterol and B-100 apolipoprotein (p=0.014, 0.001 and 0.000, respectively). When the E3/3 group was compared with E2, the same result was obtained (p=0.015, 0.002 and 0.002, respectively). The influence of the E apolipoprotein polymorphism appeared greater in female children than male.
Conclusions. The e4 allele was associated with higher levels of total cholesterol, LDL cholesterol and B-100 apolipoprotein and indicates the necessity of additional research into the interactions
between polymorphism E apolipoprotein and other genes, life styles, risk factors and potential contribution to cardiovascular diseases.
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References
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2. Ginsberg HN. Lipoprotein physiology. Endocrinol Metab Clin North Am. 1998;27:503-19.
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6. Rall SC Jr, Weisgraber KH, Mahley RW. Human apolipoprotein E. The complete amino acid sequence. J Biol Chem. 1982;257:4171-8.
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8. Hixon JE. Apolipoprotein E polymorphisms affect atherosclerosis in young males. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb. 1991;11:1237-
44.
9. Xu CF, Talmud PJ, Angelico F, Del Ben M, Savill J, Humphries SE. Apolipoprotein E polymorphism and plasma lipid, lipoprotein, and apolipoprotein levels in Italian children. Genet Epidemiol. 1991;8:389-98.
10. Srinivasan S, Ehnholm C, Wattigney W, Berenson GS. Apolipoprotein E polymorphism and its association with serum lipoprotein concentrations in black versus white children: The Bogalusa Heart Study. Metabolism. 1993;42:381-6.
11. Porkka KV, Taimela S, Kontula K, Lehtimäki T, Aalto-Setälä K, Akerblom H et al. Variability gene effects of DNA polymorphisms at the apo B, apo AI/CIII and Apo E loci on serum lipids: the Cardiovascular Risk in Young Finns Study. Clin Genet. 1994;45:113-21.
12. Sanghera DK, Ferrell RE, Aston CE, McAllister AE, Kamboh MI, Kimm SY. Quantitative effects of the apolipoprotein E polymorphism in a biracial sample of 9-10-year old girls. Atherosclerosis. 1996;126:35-42.
13. Okada T, Sato Y, Iwata F, Hara M, Kim H, Harada K. Relationship of apolipoprotein E phenotypes to serum lipid and lipoprotein levels in Japanese schoolchildren. Acta Paediatr. 1998;87:460-1.
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16. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499-502.
17. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.
18. Hixon JE, Vernier DT. Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res. 1990;31:545-8.
19. SPSS Inc. SPSS-X users guide. 3d ed. Chicago: SPSS Inc.; 1988.
20. Sing CF, Davignon J. Role of the apolipoprotein E polymorphism in determining normal plasma lipid and lipoprotein variation. Am J Hum Genet. 1985;37:268-85.
21. Bercedo Sanz A, González-Lamuño D, Muñoz P, Albajar M, Rodriguez JC, Braga S, et al. Asociación entre el perfil lipídico y genotipo de la apoproteína E en niños españoles (8-15 años). An Esp Pediatr. 1998;49:120-4.
22. Bercedo-Sanz A, González-Lamuño D, Málaga S, García-Fuentes M. Impact of apoE4 allele on total cholesterol levels of children in northern Spain. Clin Genet. 1999;55:69-70.
23. Garcés C, Cantos M, Benavente M, Granizo JJ, Cano B, Viturro E, et al. Variations in APOE genotypedistribution in children from areas with different adult cardiovascular disease mortality in Spain. Hum Biol. 2004;76:615-21.
24. Medina-Urrutia AX, Cardoso-Saldana GC, Zamora-González J, Liria YK, Posadas-Romero C. Apolipoprotein E polymorphism is related to plasma lipids and apolipoprotein in Mexican adolescents. Hum
Biol. 2004;76:605-14.
25. Sorroche P, Gutt LS, Brandi P, Oyhamburu JM, da Graca L. Fenotipos de apolipoproteína E: frecuencia y relación con los lípidos en dadores de sangre. Bioquím Pat Clin. 1997;61:277.
26. Fernández-Mestre MT, Yehirobi C, Montagnani S, Balbas O, Layrisse Z. Genetic variability of apolipoprotein E in different populations from Venezuela. Dis Markers. 2005;21:15-9.
27. De Franca E, Alves JG, Hutz MH. Apolipoprotein E polymorphism and its association with serum lipid levels in brazilian children. Hum Biol. 2004;76:267-75.
28. Lehtimäki T, Moilanen T, Viikari J, Akerblom HK, Ehnholm C, Rönnemaa T, et al. Apolipoprotein E phenotypes in Finnish youths: a cross-sectional and 6-year follow-up study. J Lipid Res. 1990;31:487-95.
29. Lehtimäki T, Porkka K, Viikari J, Ehnholm C, Akerblon HK, Nikkari T. Apolipoprotein E phenotypes and serum lipids in newborns and 3-year-old children: the Cardiovascular in Young Finns Study. Pediatrics. 1994;94:489-93.
30. Corella D, Guillén M, Sáiz C, Portolés O, Sabater A, Cortina S, et al. Environmental factors modulate the effect of the APOE genetic polymorphism on plasma lipid concentrations: ecogenetic studies in a Mediterranean Spanish population. Metabolism. 2001;50:936-44.
31. Steinmetz A, Thiemann E, Czekelius P, Kaffarnik H. Polymorphism of apolipoproteína E influences levels of serum apolipoproteína E and B in the human neonate. Eur J Clin Invest. 1989;19:390-4.
32. Herrmann W, Hanf S, Kaffarnik H, Motzny S, Reiisner J, Steinmetz A. The influence of apolipoprotein E polymorphism on plasma concentrations of apolipoprotein B and A-I during the first year of life. Pediatrics. 1994;93:296-302.
33. Garcés C, Benavente M, Lasunción MA, Ortega H, Nájera G, de Oya M. Gender-specific effects of apolipoprotein E genotype on plasma lipid levels in a population-based sample of 6-7-year-old children in Spain. Acta Paediatr. 2002;91:1039-43.
34. Reilly SL, Ferrell RE, Kottke BA, Sing CF. The gender-specific apolipoprotein E genotype influence on the distribution of plasma lipids and apolipoproteins in the population of Rochester, Minnesota, II: regression relationships with concomitans. Am J Hum Genet. 1992;51:1311-24.
35. Mänttäri M, Koskinen P, Ehnholm C, Huttunen JK, Manninen V. Apolipoprotein E polymorphism influences the serum cholesterol response to dietary intervention. Metabolism. 1991;40:217-21.
36. Schaefer EJ, Lamon-Fava S, Johnson S, Ordovas JM, Schaefer MM, Castelli W, et al. Effects of gender and menopausal status on the association of apolipoprotein E phenotype with plasma lipoprotein
levels. Arterioscler Thromb. 1994;14:1105-13.
37. Kamboh MI, Aston CE, Hamman RF. The relationship of ApoE polymorphism and cholesterol levels in normoglycemic and diabetic subjects in a biethnic population from the San Luis Valley, Colorado.
Atherosclerosis. 1995;112:145-59.
38. Mahley RW, Palaoglu KE, Atak Z, Dawson-Pepin J, Langlois AM, Cheung V, et al. Turkish heart study: lipids, lipoproteins, and apolipoproteins. J Lipid Res. 1995:36;839-59.
39. Fulton JE, Dai S, Grunbaum JA, Boerwinkle E, Labarthe DR. Apolipoprotein E affects serial changes in total and low-density lipoprotein cholesterol in adolescent girls: Project HeartBeat. Metabolism. 1999;48:285-90.
40. Kurvinen E, Aasvee K, Zordania R, Jauhiainen M, Sundvall J. Serum lipid and apolipoprotein profiles in newborns and six-year-old children: the Tallinn Young Family Study. Scand J Clin Lab Invest. 2005;65:541-50.
41. Boerwinkle E, Sing CF. The use of measured genotype information in the anaysis of quantitative phenotypes in man. III. Simultaneous estimation of the frecuencies and effects of the apolipoprotein E polymorphism and residual polygenic effects on cholesterol, betalipoproein and triglyceride levels. Ann Hum Genet. 1987;51:211-26.
42. Lund-Katz S, Wehrli S, Zaiou M, Newhouse Y, Weisgraber KH, Phillips MC. Effects of polymorphism on the microenvironment of the LDL receptor-binding region of human apoE. J Lipid Res. 2001;42:894-901.
43. Utermann G. Apolipoprotein E polymorphism in health and disease. Am Heart J. 1987;113:433-40.
2. Ginsberg HN. Lipoprotein physiology. Endocrinol Metab Clin North Am. 1998;27:503-19.
3. Mahley RW, Huang Y, Rall SC Jr. Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia). Questions, quandaries, and paradoxes. J Lipid Res. 1999;40:1933-49.
4. Das HK, McPherson J, Bruns GA, Karathanasis SK, Breslow JL. Isolation, characterization, and mapping to chromosome 19 of the human apolipoprotein E gene. J Biol Chem. 1985;260:6240-7.
5. Mahley RW. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science. 1988;240:622-30.
6. Rall SC Jr, Weisgraber KH, Mahley RW. Human apolipoprotein E. The complete amino acid sequence. J Biol Chem. 1982;257:4171-8.
7. Davignon J, Gregg RE, Sing CF. Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis. 1988;8:1-21.
8. Hixon JE. Apolipoprotein E polymorphisms affect atherosclerosis in young males. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb. 1991;11:1237-
44.
9. Xu CF, Talmud PJ, Angelico F, Del Ben M, Savill J, Humphries SE. Apolipoprotein E polymorphism and plasma lipid, lipoprotein, and apolipoprotein levels in Italian children. Genet Epidemiol. 1991;8:389-98.
10. Srinivasan S, Ehnholm C, Wattigney W, Berenson GS. Apolipoprotein E polymorphism and its association with serum lipoprotein concentrations in black versus white children: The Bogalusa Heart Study. Metabolism. 1993;42:381-6.
11. Porkka KV, Taimela S, Kontula K, Lehtimäki T, Aalto-Setälä K, Akerblom H et al. Variability gene effects of DNA polymorphisms at the apo B, apo AI/CIII and Apo E loci on serum lipids: the Cardiovascular Risk in Young Finns Study. Clin Genet. 1994;45:113-21.
12. Sanghera DK, Ferrell RE, Aston CE, McAllister AE, Kamboh MI, Kimm SY. Quantitative effects of the apolipoprotein E polymorphism in a biracial sample of 9-10-year old girls. Atherosclerosis. 1996;126:35-42.
13. Okada T, Sato Y, Iwata F, Hara M, Kim H, Harada K. Relationship of apolipoprotein E phenotypes to serum lipid and lipoprotein levels in Japanese schoolchildren. Acta Paediatr. 1998;87:460-1.
14. Ministerio de Salud, Instituto Nacional de Salud, Organización Panamericana de Salud. Situación de salud en Colombia. Indicadores básicos. Bogotá D.C.: Ministerio de Salud, Instituto Nacional de Salud, Organización Panamericana de Salud; 2002.
15. González M, De la Hoz F. Mortalidad por enfermedades crónicas no transmisibles en Colombia, 1990-1999. Inf Quinc Epidemiol Nac. 2002;14:209-36.
16. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499-502.
17. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.
18. Hixon JE, Vernier DT. Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res. 1990;31:545-8.
19. SPSS Inc. SPSS-X users guide. 3d ed. Chicago: SPSS Inc.; 1988.
20. Sing CF, Davignon J. Role of the apolipoprotein E polymorphism in determining normal plasma lipid and lipoprotein variation. Am J Hum Genet. 1985;37:268-85.
21. Bercedo Sanz A, González-Lamuño D, Muñoz P, Albajar M, Rodriguez JC, Braga S, et al. Asociación entre el perfil lipídico y genotipo de la apoproteína E en niños españoles (8-15 años). An Esp Pediatr. 1998;49:120-4.
22. Bercedo-Sanz A, González-Lamuño D, Málaga S, García-Fuentes M. Impact of apoE4 allele on total cholesterol levels of children in northern Spain. Clin Genet. 1999;55:69-70.
23. Garcés C, Cantos M, Benavente M, Granizo JJ, Cano B, Viturro E, et al. Variations in APOE genotypedistribution in children from areas with different adult cardiovascular disease mortality in Spain. Hum Biol. 2004;76:615-21.
24. Medina-Urrutia AX, Cardoso-Saldana GC, Zamora-González J, Liria YK, Posadas-Romero C. Apolipoprotein E polymorphism is related to plasma lipids and apolipoprotein in Mexican adolescents. Hum
Biol. 2004;76:605-14.
25. Sorroche P, Gutt LS, Brandi P, Oyhamburu JM, da Graca L. Fenotipos de apolipoproteína E: frecuencia y relación con los lípidos en dadores de sangre. Bioquím Pat Clin. 1997;61:277.
26. Fernández-Mestre MT, Yehirobi C, Montagnani S, Balbas O, Layrisse Z. Genetic variability of apolipoprotein E in different populations from Venezuela. Dis Markers. 2005;21:15-9.
27. De Franca E, Alves JG, Hutz MH. Apolipoprotein E polymorphism and its association with serum lipid levels in brazilian children. Hum Biol. 2004;76:267-75.
28. Lehtimäki T, Moilanen T, Viikari J, Akerblom HK, Ehnholm C, Rönnemaa T, et al. Apolipoprotein E phenotypes in Finnish youths: a cross-sectional and 6-year follow-up study. J Lipid Res. 1990;31:487-95.
29. Lehtimäki T, Porkka K, Viikari J, Ehnholm C, Akerblon HK, Nikkari T. Apolipoprotein E phenotypes and serum lipids in newborns and 3-year-old children: the Cardiovascular in Young Finns Study. Pediatrics. 1994;94:489-93.
30. Corella D, Guillén M, Sáiz C, Portolés O, Sabater A, Cortina S, et al. Environmental factors modulate the effect of the APOE genetic polymorphism on plasma lipid concentrations: ecogenetic studies in a Mediterranean Spanish population. Metabolism. 2001;50:936-44.
31. Steinmetz A, Thiemann E, Czekelius P, Kaffarnik H. Polymorphism of apolipoproteína E influences levels of serum apolipoproteína E and B in the human neonate. Eur J Clin Invest. 1989;19:390-4.
32. Herrmann W, Hanf S, Kaffarnik H, Motzny S, Reiisner J, Steinmetz A. The influence of apolipoprotein E polymorphism on plasma concentrations of apolipoprotein B and A-I during the first year of life. Pediatrics. 1994;93:296-302.
33. Garcés C, Benavente M, Lasunción MA, Ortega H, Nájera G, de Oya M. Gender-specific effects of apolipoprotein E genotype on plasma lipid levels in a population-based sample of 6-7-year-old children in Spain. Acta Paediatr. 2002;91:1039-43.
34. Reilly SL, Ferrell RE, Kottke BA, Sing CF. The gender-specific apolipoprotein E genotype influence on the distribution of plasma lipids and apolipoproteins in the population of Rochester, Minnesota, II: regression relationships with concomitans. Am J Hum Genet. 1992;51:1311-24.
35. Mänttäri M, Koskinen P, Ehnholm C, Huttunen JK, Manninen V. Apolipoprotein E polymorphism influences the serum cholesterol response to dietary intervention. Metabolism. 1991;40:217-21.
36. Schaefer EJ, Lamon-Fava S, Johnson S, Ordovas JM, Schaefer MM, Castelli W, et al. Effects of gender and menopausal status on the association of apolipoprotein E phenotype with plasma lipoprotein
levels. Arterioscler Thromb. 1994;14:1105-13.
37. Kamboh MI, Aston CE, Hamman RF. The relationship of ApoE polymorphism and cholesterol levels in normoglycemic and diabetic subjects in a biethnic population from the San Luis Valley, Colorado.
Atherosclerosis. 1995;112:145-59.
38. Mahley RW, Palaoglu KE, Atak Z, Dawson-Pepin J, Langlois AM, Cheung V, et al. Turkish heart study: lipids, lipoproteins, and apolipoproteins. J Lipid Res. 1995:36;839-59.
39. Fulton JE, Dai S, Grunbaum JA, Boerwinkle E, Labarthe DR. Apolipoprotein E affects serial changes in total and low-density lipoprotein cholesterol in adolescent girls: Project HeartBeat. Metabolism. 1999;48:285-90.
40. Kurvinen E, Aasvee K, Zordania R, Jauhiainen M, Sundvall J. Serum lipid and apolipoprotein profiles in newborns and six-year-old children: the Tallinn Young Family Study. Scand J Clin Lab Invest. 2005;65:541-50.
41. Boerwinkle E, Sing CF. The use of measured genotype information in the anaysis of quantitative phenotypes in man. III. Simultaneous estimation of the frecuencies and effects of the apolipoprotein E polymorphism and residual polygenic effects on cholesterol, betalipoproein and triglyceride levels. Ann Hum Genet. 1987;51:211-26.
42. Lund-Katz S, Wehrli S, Zaiou M, Newhouse Y, Weisgraber KH, Phillips MC. Effects of polymorphism on the microenvironment of the LDL receptor-binding region of human apoE. J Lipid Res. 2001;42:894-901.
43. Utermann G. Apolipoprotein E polymorphism in health and disease. Am Heart J. 1987;113:433-40.
How to Cite
1.
Callas N, Poveda E, Baracaldo C, Hernández P, Castillo C, Guerra M. Genetic polymorphism of the E apolipoprotein in school age children: comparison with levels of plasma lipids and apolipoproteins. biomedica [Internet]. 2007 Dec. 1 [cited 2024 May 18];27(4):526-36. Available from: https://revistabiomedica.org/index.php/biomedica/article/view/171
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