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

Polymorphisms in cytokine genes influence long-term survival differently in elderly male and female patients
Polymorphisms in cytokine genes influence long-term survival differently in elderly male and female patients
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.
0954-6820
215-223
Cederholm, T.
1d711a61-7e4d-47a1-96c4-af9948f0af3e
Persson, M.
73a926dc-10a6-40f9-88ab-0df540e2fa53
Andersson, P.
d934350b-27e7-41f8-9b79-a40d33ad35b9
Stenvinkel, P.
97ad009f-68ab-4d19-b9d3-6158c5a928b4
Nordfors, L.
4250e56a-d747-4f49-9c14-268fbbb4fd2f
Madden, J.
0771e352-d432-41ea-8a7e-4704c1efca46
Vedin, I.
fa428028-019f-4947-b099-d5c16e63ff3c
Wretlind, B.
4afab7d3-5eca-4f13-b9ed-44d882ad6379
Grimble, R.F.
3100e4d2-8f29-4ca6-a95d-38a6a764865f
Palmblad, J.
97da47d0-7fa1-4608-badf-90fe6bd8f9fe
Cederholm, T.
1d711a61-7e4d-47a1-96c4-af9948f0af3e
Persson, M.
73a926dc-10a6-40f9-88ab-0df540e2fa53
Andersson, P.
d934350b-27e7-41f8-9b79-a40d33ad35b9
Stenvinkel, P.
97ad009f-68ab-4d19-b9d3-6158c5a928b4
Nordfors, L.
4250e56a-d747-4f49-9c14-268fbbb4fd2f
Madden, J.
0771e352-d432-41ea-8a7e-4704c1efca46
Vedin, I.
fa428028-019f-4947-b099-d5c16e63ff3c
Wretlind, B.
4afab7d3-5eca-4f13-b9ed-44d882ad6379
Grimble, R.F.
3100e4d2-8f29-4ca6-a95d-38a6a764865f
Palmblad, J.
97da47d0-7fa1-4608-badf-90fe6bd8f9fe

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).

Record type: Article

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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More information

Published date: 2007
Additional Information: Online Early Article
Organisations: Dev Origins of Health & Disease, Medicine

Identifiers

Local EPrints ID: 46281
URI: https://eprints.soton.ac.uk/id/eprint/46281
ISSN: 0954-6820
PURE UUID: 7063430f-4d0f-4bc2-9e77-db93dc661d49

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Date deposited: 20 Jun 2007
Last modified: 13 Mar 2019 21:03

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