A significant relationship between PON1 promoter polymorphism and no clinical CAD signs with ageing was found in our sample, indeed justifying our data, we enrolled healthy octogenarians, who showed no reduction in PON1 activity. The mayor implication of these findings is that the (-107)CC genotype, beside to be a predictor of decreased CAD risk in younger subjects (James et al., 2000, 2001) can significantly affect the healthy ageing, delaying the progression of cardiovascular events.

Analyzing Q192R and L55M genotypes, we did not find any different distribution in both groups of subjects or any significant association between these genotypes and PON1 activity. A significant relationship between Q192R polymorphism and age-related myocardial infarction risk

Mean values ^ SD. In brackets number of patients.

S. Campo et al. / Experimental Gerontology 39 (2004) 1089–1094

(Sent`ı et al., 2001) has been recently reported, by contrast no relation between Q192R and L55M polymorphisms, CAD and cardiovascular mortality in elderly persons has been also observed (Heijmans et al., 2000). The lack of association found between Q192R and L55M polymorph- isms and PON1 activity could be partially attributed to the fact that these mutations are not causally related to atherosclerosis but are rather influenced by other functional PON1 gene polymorphisms (Leviev and James, 2000), such as T(-107)C, implicating that the promoter mutation could affect the association between PON1 192 and 55 poly- morphisms and CAD risk (James et al., 2000, 2001).

diet may provide an higher level of protection against oxidative stress (Bonanome et al., 1992; Visioli and Galli, 2001). In this case, the relative contribution of PON1 promoter polymorphism and activity to resistance to develop cardiovascular disorders might be overestimated.

In conclusion, our data provide evidence of a significant prevalence of PON1 promoter (-107)CC genotype in Sicilian octogenarians whit no clinical CAD signs. Further- more, they underline the protective role of PON1 activity and HDL-C increased values in healthy ageing and otherwise do not exclude the antioxidant protective effect of the Mediterranean diet in Sicilian population on development of atherosclerosis.

Ageing has been shown to result in a decrease of plasma HDL-C levels, however, HDL-C levels have been reported to increase in healthy elderly subjects (Nikkila and Keikkinen, 1990): this candidate HDL as a selective feature for longevity (Burke et al., 2001). HDL-C levels were higher in octogenarians than in controls, furthermore there was a significant association between HDL levels and T(-107)C genotypes in both groups, being the CC genotypes associated with the highest HDL concentration. Similarly, a significant relationship between PON1 activity and HDL-C levels occurred when these parameters were analysed in both groups (octogenarians and younger subjects) separately. PON1 activity and localization are intimately linked with HDL, nevertheless, it would be hypothesized that PON1 gene may have a role in affecting lipid metabolism and levels. Actually, several studies lack to find an association between PON1 genotype and lipid profile (Nevin et al., 1996; Xia et al., 2003), however, genetic variations in PON1 have been found to associate with variation in plasma lipoprotein traits (Saha et al., 1991; Hegele et al., 1995). Although the function of paraoxonase in lipoprotein metabolism remains an unanswered question our data could support the suggestion that PON1 gene may be a determinant of plasma lipoproteins. Further investi- gations are needed to clarify this assumption. Conversely, beneficial factors affecting HDL, such as diet, gender and life style, would be expected to influence HDL composition

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