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The Tumor Necrosis Factor Alpha −308G>A Polymorphism Is Associated with Dementia in the Oldest Old
Author(s) -
Bruunsgaard Helle,
Benfield Thomas L.,
AndersenRanberg Karen,
Hjelmborg Jacob v. B.,
Pedersen Agnes N.,
Schroll Marianne,
Pedersen Bente K.,
Jeune Bernard
Publication year - 2004
Publication title -
journal of the american geriatrics society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.992
H-Index - 232
eISSN - 1532-5415
pISSN - 0002-8614
DOI - 10.1111/j.1532-5415.2004.52369.x
Subject(s) - medicine , dementia , longevity , genotype , polymorphism (computer science) , logistic regression , cohort , allele , proportional hazards model , gerontology , danish , population , analysis of variance , demography , genetics , disease , biology , gene , linguistics , philosophy , environmental health , sociology
Objectives: To test the hypothesis that the tumor necrosis factor (TNF) −308 G>A promoter gene polymorphism is a risk factor in age‐related dementia and longevity. Design: A cross‐sectional and a longitudinal study. Setting: A population‐based sample of Danish centenarians. Participants: One hundred‐year‐old Danes (n=122) from “The Longitudinal Study of Danish Centenarians.” Octogenarians (n=174) and healthy volunteers aged 18 to 30 (n=47) served as reference groups. Methods: Whether the distribution of TNF −308 GG/GA/AA genotypes were different in centenarians than in younger age groups was investigated (Fischer exact test). Furthermore, whether the TNF −308 G>A polymorphism was associated with the prevalence of dementia (logistic regression analysis), the plasma level of TNF‐α (analysis of variance), and mortality in the following 5 years (Cox regression analysis) within the cohort of centenarians was tested. Results: The distribution of TNF −308 genotypes was not different across the three different age groups, but the GA genotype was associated with decreased prevalence of dementia in centenarians. The few centenarians with AA carrier status had higher mortality risk and tended to show higher plasma levels of TNF‐α, but the significance was questionable due to a low number of subjects with this genotype. Conclusion: It is possible that the TNF −308 A allele is maintained during aging because subjects who are heterozygous for this polymorphism possess the optimal inflammatory response with regard to protection against age‐related neurodegeneration.