4. Discussion

In the present study, we didn’t find statistically significant differences in IL-6 2174 G/C promoter genotype or allele frequencies between centenarians and middle-aged subjects from Southern Italy. This study did not provide evidence to support the suggested role of the IL-6 2174 G/C promoter polymorphism in human longevity due to a decreased frequency of the IL-6*G/*G genotype in male centenarians compared with elderly and long-lived subjects in the only other study on centenarians (Bonafe` et al., 2001).

2.3. Statistical analysis

The statistical analysis was performed by Pearson x2 test to make genotype and allele comparisons as well as test for agreement of data with Hardy–Weinberg principles. Allele frequencies were determined by allele counting. To express variances of the allele frequencies, 95% confidence intervals were used, the upper and lower values of which were calculated according to the Wilson’s formulas. To evaluate whether the association between IL6 2174 G/C promoter genotypes and longevity were homogeneous in all APOE strata we used a permutation-based exact logistic model by LogXact procedure implemented in the SAS system (Proc- LogXact 5). Statistical analysis were conducted with the SPSS software, version 11.5 (SPSS Inc., Chicago IL, USA).

associations of the IL-6*G/*G genotype with elevated circulating IL-6 plasma levels at all ages: young adults, elderly adults, and centenarians (Fishman et al., 1998; Burzotta et al., 2001; Bonafe` et al., 2001; Olivieri et al., 2002). In fact, high IL-6 concentrations were a credible predictor of increased disability and mortality in the elderly (Ferrucci et al., 1999; Harris et al., 1999; Ershler and Keller, 2000), and the IL-6*G/*G genotype was associated, probably through increased IL-6 plasma levels, with higher risk of AD (Pola et al., 2002a), MID (Pola et al., 2002b), and vascular diseases (Rauramaa et al., 2000; Burzotta et al., 2001; Flex et al., 2002). However, how the IL-6 2174 G/C promoter polymorphism modulates IL-6 plasma levels remains controversial. In fact, in vitro different models have been proposed to evaluate the influence of the IL-6 2174 G/C promoter polymorphism on IL-6 production with

3. Results

Table 2 shows IL-6 2174 G/C promoter genotype and allele frequencies in centenarians and middle-aged subjects in our population from Southern Italy. The frequencies of the different IL-6 2174 G/C promoter genotypes in our

Interleukin-6 (IL-6) promoter 2174 G/C genotype and allele distributions in centenarians and middle-aged subjects

Mean age at Genotypes n; frequency (95% CI) Alleles n; frequency (95% CI) collection (^SD) (years) IL-6*G/*G IL-6*G/*C IL-6*C/*C IL-6*G IL-6*C IL-6*C/*C Vs 100 (^2) 42 0.52 (0.62–0.41) 31 0.38 (0.49–0.28) 8 0.10 (0.18–0.05) 115 0.71 (0.77–0.64) 47 0.29 IL-6*C/*G ðn ¼ 81Þ Middle-aged 51 (^18) 78 0.64 (0.72–0.55) 37 0.30 (0.39–0.23) 7 0.06 (0.11–0.03) 193 0.79 (0.84–0.74) 51 0.21 subjects ðn ¼ 122Þ

n; number of individuals genotyped; CI, confidence interval reported in brackets; SD, standard deviation reported in brackets.

C. Capurso et al. / Experimental Gerontology 39 (2004) 1109–1114

Table 3

and nonagerian subjects compared with younger subjects of the local population, aged 20–45 years (Rea et al., 2003). This trend appeared more marked in elderly males compared with the females (Ross et al., 2003) but both groups showed an almost 10% decrease frequency in the oldest subjects. In the present study, there is a difference of 12% in the IL-6*G/*G genotype frequency between centenarians and middle-aged group (52 and 64%, respectively), though not statistically significant. ^ Concerning our control group (mean age: 51 18 SD; range: 19–73 years), some of them, will turn out to be centenarians, however this kind of overlap between the two populations cannot be expected to be rather frequent. On the contrary, in the study of Bonafe` et al. (2001), the long-lived subjects (81–99 years) appear to be somewhat overlapped in age with the centenarian group.

Interleukin-6 (IL-6) promoter 2174 G/C genotype and allele comparisons between centenarians and middle-aged subjects

Statistical analysis performed by Pearson x2 test.

environments (Terry et al., 2000; Olivieri et al., 2002; Olivieri et al., 2003). In vivo, several studies have reported that the IL-6*C/*C genotype is associated with higher levels of IL-6 (Jones et al., 2001; Kilpinen et al., 2001; Brull et al., 2001, 2002), and Rauramaa et al. (2000) found no effect of the polymorphism on baseline IL-6 plasma levels in 92 asymptomatic males.

Explanation for the conflicting findings that have been reported could be linked to variability in the strength of association that may exist between the IL-6 2174 G/C promoter polymorphism and longevity which could be modified by European regional differences in allele frequencies that we have identified for both the APOE and angiotensin I converting enzyme 1 (ACE1) genes in centenarians (Panza et al., 1999, 2003). In fact, interest- ingly, the IL-6*C allele frequency appears to vary across Europe, with an increasing trend from South to North in these very old populations: centenarians in the present study 29%, Italian centenarians 28.8% (Bonafe` et al., 2001), Irish octo/nonagenarians 45% (Rea et al., 2003), Finnish nonagerians 51% (Wang et al., 2001).