study of Bonafe` et al. on the role of IL-6 2174 G/C promoter polymorphism in centenarians (Bonafe` et al., 2001). Furthermore, two other studies have been conducted on this polymorphism in octogenarian and nonagenarian subjects (Wang et al., 2001; Rea et al., 2003). In fact, in 250 Finnish community living and hospitalized nonagenarians and 400 healthy blood donors, aged 18–60 years, there was a lack of association between human longevity and gene variants of IL-1 cluster, IL-6 2174 G/C promoter, IL10, and tumor nervous factor a, alone or in combination, though there was a reduction of 2.5% of the Il-6*G/*G frequency between nonagenarians and widely age-selected younger control group (Wang et al., 2001). On the contrary, Rea et al., in the Belfast Elderly Longitudinal Free-living Ageing STudy (BELFAST), found a trend for a reduced frequency of the IL-6*G/*G genotype in 193 octogenarian

In the present study, we did not find any statistically differences in rates between IL-6 2174 G/C alleles and centenarians among the APOE strata, view of evidence of an involvement of this polymorphism longevity (Panza et al., 2004). In fact, recently we showed the frequency of the APOE 1 4 allele was significantly

Interleukin-6 (IL-6) promoter 2174 G/C genotype and allele distributions according to apolipoprotein E (APOE) allele presence in centenarians and aged subjects

Interleukin-6 (IL-6) promoter 2174 G/C genotype and allele distributions according to apolipoprotein E (APOE) allele presence in centenarians and middle-

Genotypes n; frequency (95% CI) Alleles n; frequency (95% CI) IL-6*G/*G IL-6*G/*C IL-6*C/*C IL-6*G IL-6*C Centenarians ðn ¼ 81Þ APOE 12 11 5 5 27 15 0.52 (0.72–0.32) 0.24 (0.45–0.11) 0.24 (0.45–0.11) 0.64 (0.77–0.49) 0.36 APOE 13 71 56 11 198 78 0.51 (0.60–0.43) 0.41 (0.49–0.33) 0.08 (0.14–0.05) 0.72 (0.77–0.66) 0.28 APOE 14 2 1 0 5 1 0.67 (0.94–0.21) 0.33 (0.79–0.06) 0.00 (0.56–0.00) 0.83 (0.97–0.44) 0.17 Middle-aged subjects ðn ¼ 122Þ APOE 12 19 6 1 44 8 0.73 (0.86–0.54) 0.23 (0.42–0.11) 0.04 (0.19–0.01) 0.85 (0.92–0.73) 0.15 APOE 13 126 65 12 317 89 0.62 (0.69–0.55) 0.32 (0.39–0.26) 0.06 (0.10–0.03) 0.78 (0.82–0.74) 0.22 APOE 14 11 3 1 25 5 0.73 (0.89–0.48) 0.20 (0.45–0.07) 0.07 (0.30–0.01) 0.83 (0.93–0.66) 0.17

n; number of individuals genotyped; CI, confidence interval reported in brackets. Statistical analysis performed by a permutation-based exact logistic

number of individuals genotyped; CI, confidence interval reported in brackets. Statistical analysis performed by a permutation-based exact logistic model.

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

Bonafe`, M., Olivieri, F., Cavallone, L., Giovagnetti, S., Mayegiani, Cardelli, M., Pieri, C., Marra, M., Antonicelli, R., Lisa, R., Rizzo, Paolisso, G., Monti, D., Franceschi, C.,

A genetic predisposition to produce high levels of IL-

is detrimental longevity. Eur. J. Immunol.

,

–

Brull, D.J., Montgomery, H.E., Sanders, J., Dhamrait, S., Luong, Rumley, A., Lowe, G.D., Humphries, S.E.,

Interleukin-

g . c and

g . c promoter polymorphisms are predictors of plasma interleukin-

levels after coronary artery surgery. Arterioscler. Thromb. Vasc. Biol.

,

–

Brull, D.J., Leeson, C.P., Montgomery, H.E., Mullen, M., d

ivitiis, Humphries, S.E., Deanfield, J.E., Lesson, C.P.,

The effect the Interleukin-

-

G .C promoter gene polymorphism endothelial function in healthy volunteers. Eur. J. Clin. Invest.

–

Burzotta, F., Iacoviello, L., Di Castelnuovo, A., Glieca, F., Luciani, Zamparelli, R., Schiavello, R., Donati, M.B., Maseri, A., Possati, Andreotti, F.,

Relation of the

G/C polymorphism interleukin-

to interleukin-

plasma levels and to length hospitalization after surgical coronary revascularization. J. Cardiol.

,

–

Capurso, A., Resta, F., D’Amelio, A., Gaddi, A., Daddato, S., Galletti, Trabucchi, M., Boffelli, S., Rozzini, R., Motta, L., Rapisarda, Receputo, G., Mattace, R., Motta, M., Pansini, L., Masotti, Marchionni, N., Petruzzi, E., Bertolini, S., Agretti, M., Costelli, Mari, D., Duca, F., Ferrazzi, P., Bosi, E., Manzoni, M., Tomasello, Salvioli, G., Baldelli, M.V., Neri, M., Franceschi, C., Cossarizza, Monti, D., Varricchio, M., Gambardella, A., Paolisso, G., Baggio, Dall

estra, M., Donazzan, S., Sangiorgi, G.B., Barbagallo, M., G., Passeri, M., Fagnoni, F., Sansoni, P., Senin, U., Cherubini, Polidori, M.C., Marigliano, V., Bauco, C., Cacciafesta, M., Forconi, Guerrini, M., Boschi, S., Fabris, F., Cappa, G., Ferrario, E., Giarelli, Cavalieri, F., Stanta, G.,

Epidemiological and aspects of Italian centenarians. Arch. Gerontol. Geriatr.

,

–

Davignon, J., Gregg, R.E., Sing, C.F.,

Apolipoprotein E ism and atherosclerosis. Arteriosclerosis

,

–

Ershler, W.B., Keller, E.T.,

Age-associated increased gene expression, late-life diseases, and frailty. Annu. Rev. Med.

higher in middle-aged subjects than in centenarians, suggesting selection against 1 4 alleles. In the same study the 1 2 allele was found to be increased in centenarians although not significantly (Panza et al., 1999). In this study, we also observed and reported for the first time a significant geographic trend for increasing 1 2 allele and decreasing 1 4 allele prevalence in centenarian populations from Northern to Southern regions of Europe (Panza et al., 1999). We suggest that this geographical trend could influence the strength of association between the 1 2 allele and longevity which was recently confirmed in Finnish centenarians (Frisoni et al., 2001).

–

Burzotta, F., Iacoviello, L., Di Castelnuovo, A., Glieca, F., Luciani, N., Zamparelli, R., Schiavello, R., Donati, M.B., Maseri, A., Possati, G., Andreotti, F.,

Relation of the

G/C polymorphism of interleukin-

to interleukin-

plasma levels and to length of hospitalization after surgical coronary revascularization. Am. J. Cardiol.

,

–