Initially, haplotypes for the three single-point substitutions were assessed for 365 randomly selected participants. These preliminary results showed that there was an almost complete allelic association between the 597G allele and the 174G allele ( = 0.95), as previously reported for other populations (Georges et al., 2001; Brull et al., 2001). Consequently, the 597G polymorphism was not studied further. Table 1 shows the genotype distribution of the 174G/C polymorphisms in different age groups.

The distribution of interleukin-6 174G/C polymorphism in different age groups is shown in Table 1. The genotype distribution of the 174G/C polymorphism alone is as informative as looking at the entire haplotype in a survival analysis in this population. The entire promoter haplotype reveals that the frequency of the 174C allele only decreases with age when it is inherited together with 572G/373(A)(T). 

In summary, investigation of IL-6 promoter polymorphisms in this very large group of subjects aged 47 to 100 years indicates that a possible solitary role for IL-6 promoter variations in ageing and disease predisposition is probably fairly small, although the modest increase in the frequency of 174GG homozygotes with age indicates a weak protective effect of this genotype.Peripheral inflammation or signals from the brain? J. Neuroimmunol., Nauck, M., Winkelmann, B.R., Hoffmann, M.M., Bohm, B.O., H., Marz, W., The interleukin-G()C promoter polymorphism in the LURIC cohort showed no association with plasma coronary artery disease and myocardial infarction. J. Mol. Med., Nybo, H., Gaist, D., Jeune, B., Bathum, L., Mue, M., Pel, J.W., Christensen, K., The Danish cohort: a genetic-epidemiological nationwide survey. J. Aging Health, Pradhan, A.D., Manson, J.E., Rifai, N., Buring, J.E., Ridker, P.M., C-reactive protein, interleukin-, and the risk of developing type mellitus. JAMA, Rauramaa, R., Vaisanen, S.B., Luong, L.A., Schmidt-Trucksass, Penttila, I.M., Bouchard, C., Toyry, J., Humphries, S.E., Stromelysin- and interleukin- gene promoter polymorphisms are determinants of asymptomatic carotid artery atherosclerosis. Thromb. Vasc. Biol., Robak, T., Gladalska, A., Stepien, H., Robak, E., Serum of interleukin-type cytokines and soluble interleukin-receptor in patients with rheumatoid arthritis. Mediators Inflamm., Sham P.C. and Curtis D. introduced Monte-Carlo tests for associations between disease and alleles at highly polymorphic loci. Ann. Hum. Genet.(Pt), Skytthe A., Kyvik K.O., Holm N.V.. Vaupel J.W.. Christensen K.. The Danish Twin Registry: 127 birth cohorts of twins. Twin Res., Terry, C.F., Loukaci, V., Green, F.R., Cooperative influence of genetic polymorphisms on interleukin-transcriptional regulation. Biol. Chem., Tschentscher, F., Kalt, A., Hoffmann, V., Epplen, J., Hardt, C., Identification and efficient genotyping of an (A)n/(T)m within the untranslated region of the human IL-gene. Eur. Immunogenet., Villuendas, G., San Millan, J.L., Sancho, J., Escobar-Morreale, The G A and G C polymorphisms in the promoter of the IL-gene are associated with hyperandrogenism. Clin. Endocrinol. Metab., We thank Shuxia Li and Alice Jensen for technical assistance. This work was supported by grants from the US National Institute on Aging (grant NIA-P01-AG08761) and the Danish Medical Research Council. References Andersen-Ranberg, K., Schroll, M., Jeune, B., Healthy centenarians do not exist, but autonomous centenarians do: a population-based study of morbidity among Danish centenarians. J. Am. Geriatr. Soc., Barbieri, M., Ferrucci, L., Ragno, E., Corsi, A., Bandinelli, S., Bonafe, M., Olivieri, F., Giovagnetti, S., Franceschi,C . ,Guralnik,J.M . ,Paolisso,G . ,Chronic inflammation and the effect of IGF-I on muscle strength and power in older persons. Am. J. Physiol. Endocrinol. Metab.(EE), Bonaccorso S et al presented serotonin-immune interactions in elderly volunteers and in patients with Alzheimer's disease (DAT): lower plasma tryptophan availability to the brain in the elderly and increased serum interleukin- in DAT. Aging (Milano), Brull, D.J., Montgomery, H.E., Sanders, J., Dhamrait, S., Luong, L., Rumley, A., Lowe, G.D., Humphries, S.E., Interleukin-gene g>c and g>c promoter polymorphisms are strong predictors of plasma interleukin-levels after coronary artery bypass surgery. Arterioscler. Thromb. Vasc. Biol., Bruunsgaard, H., Andersen-Ranberg, K., Jeune, B., Pedersen, A.N., Skinhoj, P., Pedersen, B.K., A high plasma concentration of TNF-alpha is associated with dementia in centenarians. J. Gerontol. A Biol. Sci. Med. Sci.(MM), Bruunsgaard H et al discussed aging and proinflammatory cytokines. Curr. Opin. Hematol., Chakravarti A et al examined nonuniform recombination within the