Polymorphisms in cytokine genes influence long-term survival differently in elderly male and female patients

Cederholm T, Persson M, Andersson P, Stenvinkel P, Nordfors L, Madden J, Vedin I, Wretlind B, Grimble RF, Palmblad J (Uppsala University Hospital, Sweden; University of Southampton School of Medicine, Southampton, UK; and Karolinska University Hospital, Stockholm, Sweden). Polymorphisms in cytokine genes influence long-term survival differently in elderly male and female patients. J Intern Med 2007; 262: 215-223. Objectives. We asked if single nucleotide polymorphisms (SNP) in inflammatory cytokine genes related to 3-year survival in ill elderly subjects and if genotypes differed between the elderly and a younger control population. Design. Prospective observational study. Setting. Two geriatric departments at a university hospital. Subjects. Eighty three acutely admitted geriatric patients (83 +/- 7 year, 70% women) and 207 young healthy subjects (40 1 year, 37% women) were included. Outcome measures. Single nucleotide polymorphisms in the genes of tumour necrosis factor (TNF)-alpha -308 G/A, interleukin (IL)-1 beta -511 C/T, IL-6 -174 G/C and IL-10 -1082 A/G were analysed. In the geriatric patients SNP in lymphotoxin (LT)-alpha +252 G/A and serum levels of TNF-alpha, IL-6, IL-10, soluble IL-I receptor(R)II were also determined, as well as the 3-year mortality. Results. The allele distribution did not differ significantly between the elderly and the young. In the female elderly, 3-year survival was doubled (P < 0.05) in those with the high-producing genotypes of IL-6 -174 GG and TNF-alpha -308 GA compared with those with low-producing alleles. In contrast, men with high-producing LT-alpha +252 AA and IL-1 beta -511 CT&TT genotypes displayed halved 3-year survival (P < 0.05) compared with those with low-producing genotypes, whereas possession of the high-producing IL-10 -1082 GG genotype favoured survival. Serum IL-10 was higher in the high-producing IL-10 genotype in females. Conclusion. As high-producing IL-6 -174 genotype favoured 3-year survival in women, whereas the likewise high-producing LT-a +252 and IL-1 beta -511 genotypes were associated with poor survival in men, we conclude that the specific genotypes, in association with gender, may act as determinants for survival in elderly patients.