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


METHODS
Prospective observational study.


METHODS
Two geriatric departments at a university hospital.


METHODS
Eighty three acutely admitted geriatric patients (83 +/- 7 year, 70% women) and 207 young healthy subjects (40 +/- 1 year, 37% women) were included.


METHODS
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.


CONCLUSIONS
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.
Cederholm
T
T
Department of Public Health and Caring Sciences, Uppsala University Hospital, Uppsala, Sweden. tommy.cederholm@pubcare.uu.se
Persson
M
M
Andersson
P
P
Stenvinkel
P
P
Nordfors
L
L
Madden
J
J
Vedin
I
I
Wretlind
B
B
Grimble
R F
RF
Palmblad
J
J
D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000097:blood / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007378:Interleukins / Q000097:blood / Q000235:genetics; D008136:Longevity / Q000235:genetics*; D008233:Lymphotoxin-alpha / Q000097:blood / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D053574:Receptors, Interleukin-1 Type II / Q000097:blood / Q000235:genetics; D012737:Sex Factors; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics
D016207:Cytokines; D007378:Interleukins; D008233:Lymphotoxin-alpha; D053574:Receptors, Interleukin-1 Type II; D014409:Tumor Necrosis Factor-alpha