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

J Intern Med. 2007 Aug;262(2):215-23. 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)-alpha-308 G/A, interleukin (IL)-1beta-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-1beta-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-alpha +252 and IL-1beta -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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cytokines / blood
  • Cytokines / genetics*
  • Female
  • Genotype
  • Humans
  • Interleukins / blood
  • Interleukins / genetics
  • Longevity / genetics*
  • Lymphotoxin-alpha / blood
  • Lymphotoxin-alpha / genetics
  • Male
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, Interleukin-1 Type II / blood
  • Receptors, Interleukin-1 Type II / genetics
  • Sex Factors
  • Survival Analysis
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Cytokines
  • Interleukins
  • Lymphotoxin-alpha
  • Receptors, Interleukin-1 Type II
  • Tumor Necrosis Factor-alpha