The effect of Apo E polymorphism on plaSma total Chol, LDL -Chol and Apo B values (adjusted for ~x and age) was evaluated by analysis of covariance [fable 4). The numbers of £3 ed £4 alleles were introduced as ex plicative variables. Since the number of the three possible alleles in the genotype is not independent, the effect of more than two cannot be evaluated Simultaneously.

Table 3 - Variation of Apo E allele frequency with age.

A significant association was observed between £4 and all the lipid parameters, whereas £3 was signifi cantly associated with LDL-Chol only, and more weak ly with the other parameters.

Age ,;;;65 66-70 71-75 >76 p * N=165 N=32 N=19 N=12 £2 7.58 6.25 5.00 4.55 0.418 £3 80.60 84.37 92.50 95.45 0.013 £4 11.82 9.38 2.50 0.00 0.015

The results of this study of genetically determined Apo E polymorphism and its role with regard to

'p value for a Mantel-Haenszel X2 test for trend.

Table 4 - Covariance analysis of lipoproteins lIS number of f.3 and e4 alleles, adjusted for sex and age.

concerning the association between £4 and LDL hy percholesterolemia, and hence an increased inci dence of cardiovascular disease, and the assumption that the E phenotype, in any case, is important in as sessing the risk of atherosclerosis in patients with high LDL-Chollevels. Indeed, compared with other phenotypes, the reduced frequency of £4 during aging in relation to increased mortality, at present may on ly support speculative hypotheses. One must not lose sight of the fact that other adverse factors may be as sociated with Apo E alleles, especially the E3/ 4 phe notype, such as the different process times of chy lomicra and remnant particles, with an influence on the residence times of atherogenic particles in the cir culation and on HDL-Chollevels (30), together with uncertain effects on clotting parameters. Besides, a demonstrated association exists between £4 and en hanced plasma lipoprotein(a) (31). Previous papers have also described a close association between £4 and type V hyperlipoproteinemia (32, 33).

b p value Serum Chol Age 0.84 0.0001 Sex 11.65 0.0569 E4 23.51 0.0169 e3 14.52 0.0695 LOGTg Age 0.009 0.0001 Sex -0.173 0.0141 £4 0.224 0.0471 £3 0.149 0.1040 LDL-Chol Age 0.604 0.0006 Sex 9.987 0.0648 £4 22.660 0.0093 £3 14.908 0.0352 Apo B Age 0.863 0.0001 Sex 6.696 0.1024 E4 14.817 0.0246 £3 7.998 0.1354

These metabolic features of the Apo E phenotype need to be carefully investigated before the effect of al lele £4 on the deterioration of lipoproteic metabolism, and its early disappearance during aging can be clear ly assessed.

ACKNOWLEDGEMENTS

This work was supported in part by a grant from the "Consiglio Nazionale delle Ricerche" (n.93.00432.PF40, Progetio Finalizzato "lnvecchiamento") and the "Ministero dell'Universita e della Ricer ca Scientifica e Tecnologica", Roma, Italy. We are also indebted to Immuno, Vienna, for sheep Anti-Apo E antibody supplement.

b= regression coefficient, i.e., increase in lipid value as a consequence of a unit increase in the explaining variable (in the case of sex, males us females). p value= significance of the t test for regreSSion coefficient = 0

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