Discussion

Lifespan is the result of multiple processes involving environmental factors and many plausible candidate genetic factors, thus some human genetic studies have investigated putative associations, but only a few replica- tions have been observed across human populations. The main problems of ‘‘longevity’’ case/control association studies are the small sample size, the lack of precise phe- notyping and variations in ethnic population stratification; thus it is important to replicate any positive findings, especially if detected in different ethnic groups, to reach reliable conclusions on the effect that putative candidate genes have on longevity.

Results

To date, there is only one study on the role played by the ATM gene in longevity in the Chinese population and our data report, for the first time, the association of the ATM gene variation in Caucasian LLIs.

We examined the distribution of the C/T genotype fre- quencies with respect to the other genotypes (C/C ? T/T) in the LLI group compared to the controls, due to a dose-

Our study, having a 78.9 % power to detect an OR of 2.0 at a 5 % significance rate, confirms in Italian cente- narians the role of the rs189037C/T genotype in the ATM gene promoter previously described in Chinese nonagenarians/centenarians [8]. Despite the small number of enrolled subjects, our result is quite reliable. All par- ticipants are from the same restricted geographical area (a small region in Central Italy) and the confounding factors are not present, thus we can speculate that predominantly genes influence longevity.

Table 1 Demographic characteristics of all studied subjects

Controls, Centenarians, N (%) N (%) Total 150 128 Age at examination 67.2 ± 9.1 98.6 ± 5.1; 52.3 % aged (mean ± SD) 100 years Gender Females 85 (56.6) 99 (77.3); 55.5 % aged 100 years Males 65 (43.3) 29 (22.6); 41.4 % aged 100 years

The genetic basis of longevity could improve the understanding of the central mechanisms of ageing and

N CC ? TT N (%) CT N (%) p value OR (95 % CI) Controls 150 90 (60 %) 60 (40 %) LLI total 128 65 (50.8 %) 63 (49.2 %) 0.12 1.45 (0.88–2.41) LLI C100 years old (centenarians) 67 30 (44.7 %) 37 (55.3 %) 0.037* 1.85 (0.99–3.45) LLI\100 years old 61 35 (57.3 %) 26 (42.7 %) 0.72 1.11 (0.58–2.13)

* Statistically significant

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Acknowledgments This study was supported by grant from the the Ministry of Health 2009 B7ASKP_003.

Conflict of interest All authors declare the absence of any conflict of interest.

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