The tumor necrosis factor alpha -308G>A polymorphism is associated with dementia in the oldest old.
OBJECTIVE
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.


METHODS
A cross-sectional and a longitudinal study.


METHODS
A population-based sample of Danish centenarians.


METHODS
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-alpha (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-alpha, but the significance was questionable due to a low number of subjects with this genotype.


CONCLUSIONS
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.
Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. hellebkemp@os.dk
Helle
H
Bruunsgaard
Thomas L
TL
Benfield
Karen
K
Andersen-Ranberg
Jacob v B
Jv
Hjelmborg
Agnes N
AN
Pedersen
Marianne
M
Schroll
Bente K
BK
Pedersen
Bernard
B
Jeune
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003430:Cross-Sectional Studies; D003704:Dementia / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha