The combinations of TNFalpha-308 and IL-6 -174 or IL-10 -1082 genes polymorphisms suggest an association with susceptibility to sporadic late-onset Alzheimer's disease.
OBJECTIVE
Single nucleotide polymorphisms in the regulatory regions of the cytokine genes for tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6 and IL-10 have been suggested to influence the risk of Alzheimer's disease (AD) with conflicting results.


OBJECTIVE
To investigate the TNFalpha-308, IL-6 -174 and IL-10 -1082 gene polymorphisms as susceptibility factors for AD.


METHODS
We analyzed genotype and allele distributions of these polymorphisms in 101 sporadic AD patients and 138 healthy controls.


RESULTS
Heterozygotes (AG) or combined genotype (AG+AA) for IL-10 -1082 were associated with approximately two-fold increase in the risk of AD. Carriers of A alleles of both TNFalpha-308 and IL-10 -1082 had 6.5 times higher risk for AD in comparison with non-carriers. Concomitant presence of both mutant TNFalpha-308 A and IL-6 -174 C alleles raised three-fold the AD risk, whereas there was no notable risk for AD afflicted by IL-6 -174 polymorphism alone.


CONCLUSIONS
Our results suggest that TNFalpha and IL-10 promoter polymorphism might be a risk factor for AD. The combined effects of TNFalpha-308, IL-6 -174 and IL-10 -1082 variant alleles may be more decisive to induce functional differences and modify the risk for AD.
Vural
P
P
Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Capa, 34093, Istanbul, Turkey. pervinvural@yahoo.com
Değirmencioğlu
S
S
Parildar-Karpuzoğlu
H
H
Doğru-Abbasoğlu
S
S
Hanagasi
H A
HA
Karadağ
B
B
Gürvit
H
H
Emre
M
M
Uysal
M
M
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10