The combinations of TNF alpha-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 (TNF alpha), interleukin (IL)-6 and IL-10 have been suggested to influence the risk of Alzheimer's disease (AD) with conflicting results. Aim-To investigate the TNF alpha-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 TNF alpha-308 and IL-10-1082 had 6.5 times higher risk for AD in comparison with non-carriers. Concomitant presence of both mutant TNF alpha-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. Conclusion-Our results suggest that TNF alpha and IL-10 promoter polymorphism might be a risk factor for AD. The combined effects of TNF alpha-308, IL-6-174 and IL-10-1082 variant alleles may be more decisive to induce functional differences and modify the risk for AD.