LETTER TO THE EDITOR
Apolipoprotein E genotype and coronary heart disease
Alberto Batalla, MDa,
Ruth Alvarez, PhDb,
Sergio Hevia, MDb,
Julián R. Reguero, MDb and
Eliecer Coto, PhDb
a Department of Cardiology, Cabueñes Hospital, Gijon, Spain
b Department of Cardiology, Laboratory of Molecular Genetics, Central Hospital of Asturias, Oviedo, Spain
We have read with interest the article by Frikke-Schmidt et al. (1), which concludes that male carriers of the Apo E epsilon43 and epsilon44 genotypes are particularly susceptible to ischemic heart disease.
We studied 220 men younger than 50 years of age (mean age 43 ± 5 years; range 26 to 50 years) and diagnosed with coronary artery disease (CAD). The polymorphisms of the apolipoprotein E (Apo E) were determined and compared to a control group of 200 healthy individuals matched with patients for age and ethnicity and residents in the same region (Asturias, northern Spain). We analyzed the principal cardiovascular risk factors, and during hospitalization and after fasting for 12 h a lipid profile study was carried out.
The Apo E genotype frequencies are summarized in Table 1. In our population, the Apo E gene and genotype frequencies were similar between patients and controls. Also, Apo E gene and genotype frequencies did not differ between patients with or without diabetes, or with or without hypertension. In addition, average biochemical values did not differ between the genotypes of each of the four polymorphisms.
Compared to other Caucasian populations, we found a lower frequency of the Apo E 4 allele. These data are in agreement with previous reports that showed the lowest frequency for the 4 allele in Southern European populations (2–6). The low frequency of the 4-frequency allele among Mediterraneans has been linked with a decreased risk of CAD in these populations, compared to Northern Europeans, who have the highest 4-frequency and the highest rate for CAD in Europe.
In accord with this, we did not find a significant difference for the Apo E gene and genotype frequencies between patients and controls, suggesting that the 4 allele is not a strong risk factor for early CAD in our population. The role of Apo E genotypes in the risk of CAD has been analyzed previously (7,8).
For the 4-allele, a significantly increased frequency in patients compared to healthy controls has been described in some but not all studies. These discrepancies could be partly attributed to the fact that these studies analyzed different populations worldwide, and the 4-allele could be a risk factor in association with other genetic or environmental factors.
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References
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1. Frikke-Schmidt R, Tybjaerg-Hansen A, Steffensen R, Jensen G, Nordestgaard BG. Apolipoprotein E genotype: epsilon32 women are protected while epsilon43 and epsilon44 men are susceptible to ischemic heart disease. J Am Coll Cardiol. 2000;35:1192–1199[Abstract/Free Full Text]
2. James RW, Boemi M, Giansanti R, Fumelli P, Pometta D. Underexpression of the apolipoprotein E4 isoform in an Italian population. Arterioscler Thromb. 1993;13:1456–1459[Abstract/Free Full Text]
3. Valveny N, Esteban E, Kandil M, Moral P. Apo E polymorphism in Spanish and Moroccan populations. Clin Genet. 1997;51:354–356[Medline]
4. Muros M, Rodriguez-Ferrer C. Apolipoprotein E polymorphism influence on lipds, apolipoproteins and Lp(a) in a Spanish population underexpressing apo E4. Atherosclerosis. 1996;121:13–21[CrossRef][Medline]
5. Tiret L, de Knijff P, Menzel H, Ehnholm C, Nicaud V, Havekes LM. Apo E polymorphism and predisposition to coronary heart disease in youths of different European populations: the EARS study. Arterioscler Thromb. 1994;14:1617–1624[Abstract/Free Full Text]
6. Van Bockxmeer FM, Mamotte CDS. Apolipoprotein epsilon homozygosity in young men with coronary heart disease. Lancet. 1992;340:879–880[CrossRef][Medline]
7. Wilson PWF, Myers RH, Larson MG, Ordovas JM, Wolf PA, Schaefer EJ. Apolipoprotein E alleles, dyslipemia and coronary heart disease: the Framingham Offspring Study. JAMA. 1994;272:1666–1671[Abstract/Free Full Text]
8. Ilveskoski E, Perola M, Lehtimäki T, et al. Age-dependent association of apolipoprotein E genotype with coronary and aortic atherosclerosis in middle-aged men. Circulation. 1999;100:608–613[Abstract/Free Full Text]
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References