Abstract
Polymorphisms of apoE gene are able to modulate lipoprotein metabolism at different steps and to influence LDL-cholesterol (LDL-C) levels and also other lipoproteins features. Population studies documented large differences in the frequency of apoE alleles which could be even related to the prevalence of cardiovascular disease. In this study we evaluated the apoE genotypes and allele frequency in 576 subjects living in a small island in the Tyrrhenian Sea and the relative contribution of apoE polymorphism on plasma lipid and lipoprotein profile, including LDL particle size. We found a cumulative frequency of 0.073, 0.866 and 0.061 for ε2, ε3 and ε4 alleles respectively. Moreover ε3 subjects had only triglyceride levels significantly lower and LDL-C and lipoprotein (a) (Lp(a)) levels higher than ε2 carriers. LDL-particle size was significant smaller in ε2 subjects than both ε3 and ε4 carriers, but the difference disappeared when data were adjusted for triglycerides. In conclusion we have provided further evidence of a low prevalence of ε4 allele in a Mediterranean population which may represent a genetic protective factor of these populations. Environmental factors, such as diet, occurring in this area may have attenuated the influence of this gene on plasma lipoproteins.
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References
Prediction of coronary heart disease in Europe. The 2nd report of the WHO-ERICA Project. ERICA Research Group. Eur Heart J 1991; 12: 291–297.
Lusis AJ. Genetic factors a.ecting blood lipoproteins: The candidate gene approach. J Lipid Res 1988; 29: 397–405.
Humphries SE. DNA polymorphisms of the apolipoprotein genes. Their use in the investigation of the genetic component of hyperlipidaemia and atherosclerosis. Atherosclerosis 1988; 72: 89–108.
Mahley RW. Apolipoprotein E: Cholesterol transport protein with expanding role in cell biology. Science 1988; 240: 622–630.
Barbagallo CM, Fan J, Blanche PJ, Rizzo M, Taylor JM, Krauss RM. Overexpression of human hepaticlipase and apoprotein E in transgenicrabbits attenuates response to dietary cholesterol and alter lipoprotein subclass distributions. Arterioscl Thromb Vasc Biol 1999; 19: 625–632.
Zannis VI, Breslow JL, Utermann G, et al. Proposed nomenclature of apoE isoproteins, apoE genotypes, and phenotype. J Lipid Res 1982; 23: 911–914.
Davignon J, Gregg RE, Sing CF. Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 1988; 8: 1–21.
Haffner SM, Stern MP, Miettinen H, Robbins D, Howard B. Apolipoprotein E polymorphism and LDL size in a biethnicpopulation. Arterioscler Thromb Vasc Biol 1996; 16: 1184–1188.
Dart AM, Cooper B. Independent effects of ApoE phenotype and plasma triglyceride on lipoprotein particle sizes in the fasting and postprandial states. Arterioscler Thromb Vasc Biol 1999; 19: 2465–2473.
Ordovas JM, Litwack-Klein L, Wilson PW, Schaefer MM, Schaefer EJ. Apolipoprotein E isoform phenotyping methodology and population frequency with identi.cation of apoE1 and apoE5 isoforms. J Lipid Res 1987; 28: 371–380.
Robitaille N, Cormier G, Couture R, Bouthillier D, Davignon J, Perusse L. Apolipoprotein E polymorphism in a French Canadian population of northeastern Quebec: Allele frequencies and e.ects on blood lipid and lipoprotein levels. Hum Biol 1996; 68: 357–370.
Ehnholm C, Lukka M, Kuusi T, Nikkila E, Utermann G. Apolipoprotein E polymorphism in the Finnish population: Gene frequencies and relation to lipoprotein concentrations. J Lipid Res 1986; 27: 227–235.
De Knij. P, Johansen LG, Rosseneu M, Frants RR, Jespersen J, Havekes LM. Lipoprotein profile of a Greenland Inuit population. In.uence of anthropo-metricvariables, ApoE and A4 polymorphism, and lifestyle. Arterioscl Thromb 1992; 12: 1371–1379.
Hallmann DM. The apolipoprotein E polymorphism, a comparison of allele frequencies and effects in nine population. Am J Hum Genet 1991; 49: 338–349.
Pedersen JC, Berg K. Interaction between low density lipoprotein receptor (LDLR) and apolipoprotein E (apoE) alleles contributes to normal variation in lipid level. Clin Genet 1989; 35: 331–337.
Luc G, Bard JM, Arveiler D, et al. Impact of apolipoprotein E polymorphism on lipoproteins and risk of myocardial infarction. The ECTIM Study Arterioscl Thromb VascBiol 1994; 14: 1412–1419.
Mahley RW, Palaoglu KE, Atak Z, et al. Turkish Heart Study: Lipids, lipoproteins, and apolipoproteins. J Lipid Res 1995; 36: 839–859.
Kao J-T, Tsai KS, Chang CJ, Huang PC. The e.ects of apolipoprotein E polymorphism on the distribution of lipids and lipoproteins in the Chinese population. Atherosclerosis 1995; 114: 55–59.
Gomez-Coronado D, Alvarez JJ, Entrala A, Olmos JM, Herrera E, Lasuncion MA. Apolipoprotein E polymorphism in men and women from a Spanish population: Allele frequencies and in.uence on plasma lipids and apolipoproteins. Atherosclerosis 1999; 147: 167–176.
James RW, Boemi M, Giansanti R, Fumelli P, Pometta D. Underexpression of the apolipoprotein E4 isoform in an Italian population. Arterioscl Thromb 1993; 13: 1456–1459.
Corbo RM, Scacchi R, Mureddu L, Mulas G, Alfano G. Apolipoprotein E polymorphism in Italy investigated in native plasma by a simple polyacrylamide gel isoelectric focusing technique. Comparison with frequency data of other European populations. Ann Hum Genet 1995; 59: 197–209.
Deiana L, Pes GM, Carru C, et al. Lack of in.uence of apolipoprotein E4 on lipoprotein levels in the island population of Sardinia. Eur J Clin Invest 1998; 28: 290–294.
Hixson JE, Vernier DT. Restriction isotyping of human apolipoprotein E by gene ampli.cation and cleavage with HhaI. J Lipid Res 1990; 31: 545–548.
Krauss RM, Burke DJ. Identi.cation of multiple subclasses of plasma low density lipoproteins in normal humans. J Lipid Res 1982; 23: 97–104.
Asakawa J, Takahashi N, Rosenblum BB, Neel JV. Two-dimensional gel studies of geneticvariation in the plasma proteins of Amerindians and Japanese. Hum Genet 1985; 70: 222–230.
Kamboh MI, Aston CE, Ferrell RE, Hamman RF. Impact of apolipoprotein E polymorphism in determining interindividual variation in total cholesterol and low density lipoprotein cholesterol in Hispanics and non-Hispanicwhites. Atherosclerosis 1993; 98: 201–211.
Scheer WD, Boudreau DA, Malcom GT, Middaugh JP. Apolipoprotein E and atherosclerosis in Alaska Natives. Atherosclerosis 1995; 114: 197–202.
Gerdes LU, Klausen IC, Sihm I, Faergeman O. Apolipoprotein E polymorphism in a Danish population compared to findings in 45 other study populations around the world. Genet Epidemiol 1992; 9: 155–167.
Smit M, De Knij. P, Rosseneu M, et al. Apolipoprotein E polymorphism in The Netherlands and its e.ect on plasma lipid and apolipoprotein levels. Hum Genet 1988; 80: 287–292.
Braeckman L, De Bacquer D, Rosseneu M, De Backer G. Apolipoprotein E polymorphism in middle-aged Belgian men: Phenotype distribution and relation to serum lipids and lipoproteins. Atherosclerosis 1996; 120: 67–73.
Lenzen HJ, Assmann G, Buchwalsky R, Schulte H. Association of apolipoprotein E polymorphism, lowdensity lipoprotein cholesterol, and coronary artery disease. Clin Chem 1986; 32: 778–781.
Kowalska A, Wiechmann I, Walter H. Genetic variability of apolipoprotein E in a Polish population. Hum Biol 1998; 70: 1093–1099.
Nagy B, Karadi I, Fintor L, Rigo J Jr, Romics L, Papp Z. Apolipoprotein E gene polymorphism frequencies in a sample of healthy Hungarians. Clin Chim Acta 1999; 282: 147–150.
Cariolou MA, Kokkofitou A, Manoli P, Christou S, Karagrigoriou A, Middleton L. Underexpression of the apolipoprotein E2 and E4 alleles in the Greek Cypriot population of Cyprus. Genet Epidemiol 1995; 12: 489–497.
Sklavounou E, Economou-Petersen E, Karadima G, et al. Apolipoprotein E polymorphism in the Greek population. Clin Genet 1997; 52: 216–218.
Eto M, Watanabe K, Ishi K. A racial di.erence in apolipoprotein E allele frequencies between the Japanese and Caucasian populations. Clin Genet 1986; 30: 422–427.
Gounden N, Naidoo J, Pegoraro RJ, Berger GM. Apolipoprotein E allele frequencies in a South African Indian female population. Clin Genet 1995; 48: 243–245.
Motti C, Gnasso A, Pujia A, et al. Genotype distribution of apoE polymorphism in a sample of population from Calabria. Atherosclerosi 1997; 135(Suppl 1): S16 (Abstract).
Gallo S, Barbagallo CM, Averna MR, et al. ApoE genotype in a low-cholesterol mediterranean population of southern Italy. Atherosclerosis 1997; 135(Suppl 1): S13 (Abstract).
Wilson PWF, Schaefer EJ, Larson MG, Ordovas JM: Apolipoprotein E alleles and risk of coronary disease. A meta-analysis. Arterioscler Thromb Vasc Biol 1996; 16: 1250–1255.
Kosunen O, Talasniemi S, Lehtovirta M, et al. Relation of coronary atherosclerosis and apolipoprotein E genotypes in Alzheimer patients. Stroke 1995; 26: 743–748.
Barbagallo CM, Cavera G, Sapienza M, et al. Prevalence of overweight and obesity in a rural southern Italy population and relationships with total and cardiovascular mortality: The Ventimiglia di Sicilia project. Int J Obes 2001; 25: 185–190.
De Knij. P, Kaptein A, Boomsma D, Princen HM, Frants RR, Havekes LM. Apolipoprotein E polymorphism a.ects plasma levels of lipoprotein(a). Atherosclerosis 1991; 90: 169–174.
Miettinen T, Gylling H, Vanhanen H, Ollus A. Cholesterol absorption, elimination, and synthesis related to LDL kinetics during varying fat intake in men with di.erent apoprotein E phenotypes. Arterioscl Thromb 1992; 12: 1044–1052.
Krauss RM. Heterogeneity of plasma low-density lipoproteins and atherosclerotic risk. Curr Opin Lipidol 1994; 5: 339–349.
Schaefer EJ, Lamon-Fava S, Johnson S. Effects of gender and menopausal status on the association of apolipoprotein E phenotype with plasma lipoprotein levels. Results from the Framingham o.spring study. Arterioscler Thromb 1994; 14: 1105–1113.
Zhao SP, Verhoeven MH, Vink J, et al. Relationship between apolipoprotein E and low density lipoprotein particle size. Atheroslerosis 1993; 102: 147–154. Address for correspondence: Dr Carlo M. Barbagallo, Istituto di Medicina Interna e Geriatria, Policlinico ‘Paolo Giaccone’, Via del Vespro 141, I-90127 Palermo, Italy Phone: +39-91-6552891; Fax: +39-91-6552957 E-mail: carlob@unipa.it 713
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Barbagallo, C., Polizzi, F., Severino, M. et al. ApoE polymorphism in a small Mediterranean island: Relationships with plasma lipids, lipoproteins and LDL particle size. Eur J Epidemiol 17, 707–713 (2001). https://doi.org/10.1023/A:1015618216828
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DOI: https://doi.org/10.1023/A:1015618216828