Further studies are needed to elucidate the role of the CETP variant in longevity. Due to the difficulties to recruit subjects of an extreme age, there is the need to plan a joined study analyzing larger samples of long-lived individuals from different populations, evaluating the correlation between the biological, clinical phenotype and the genotype. This should clarify if a CETP genotype is necessary or/and sufficient for successful aging or if such an association oscillates according to the various ethnic backgrounds and/ or other unknown sources of stratification.

The genotype and allele frequency distributions (Table 1), conforming to the Hardy-Weinberg equilibrium ( p > 0.05), were similar for the long-lived subjects and controls. The VV genotype (8.6%) and V allele (31%) frequencies in the Italian long-lived subjects differs from those previously reported by Barzilai and coworkers (24.8% for the VV genotype and 46% for the V allele) in Askenazi Jewish centenarians thus suggesting genetic heterogeneity among populations. We report here the lack of association of the valine (V) allele in the long-lived subjects. In fact a slight although not significant reduction in the Vallele (x2 = 1.75; p = 0.18) and VV genotype (x2 = 0.24; p = 0.63) frequen- cies was observed in centenarians.

Acknowledgments

Our genetic study on Italian centenarians does not confirm the association between the I405V CETP variation and the healthy aging phenotype described in the Ashkenazi Jewish population. A further possible explanation for the inconsistency between our results and those mentioned above (Barzilai et al., 2003) may be that the CETP polymorphism is in linkage disequilibrium with another closed gene. We could not exclude that our result may represent a false-negative finding which is a common limitation in association studies. However, the sample size analysis demonstrated 73% power (odds ratio = 2, 5% significance) to test differences, providing evidence that our study is not underpowered and is able to detect even a marginal genetic effect of the allelic variants on phenotype. Several polymorphisms have been reported in the

This study was supported by grants from the Italian Ministry of Instruction, University and Research (Grant no. RBNE018R89, Prof. Sorbi) as well as from the EU 5FP FUNTIONAGE project (Dr. Franceschi) and the Italian Ministry of Health (Genetic and Non-genetic Factors of Health in the Elderly) (Dr. Franceschi).

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