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, R.F. and Palmblad, J. (2007) Polymorphisms in cytokine genes influence long-term survival differently in elderly male and female patients. Journal of Internal Medicine, 262 (2), 215-223. (doi:10.1111/j.1365-2796.2007.01803.x).

Abstract

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)-?–308 G/A, interleukin (IL)-1?–511 C/T, IL-6–174 G/C and IL-10–1082 A/G were analysed. In the geriatric patients SNP in lymphotoxin (LT)-? +252 G/A and serum levels of TNF-?, 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-? -308 GA compared with those with low-producing alleles. In contrast, men with high-producing LT-? +252 AA and IL-1?–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-? +252 and IL-1? -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.

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