The combinations of TNFα–308 and IL-6 –174 or IL-10 –1082 genes polymorphisms suggest an association with susceptibility to sporadic late-onset Alzheimer’s disease
Vural P, Değirmencioğlu S, Parıldar-Karpuzoğlu H, Doğru-Abbasoğlu S, Hanagasi HA, Karadağ B, Gürvit H, Emre M, Uysal M. The combinations of TNF[alpha][ndash]308 and IL-6[ndash]174 or IL-10 [ndash]1082 genes polymorphisms suggest an association with susceptibility to sporadic late-onset Alzheimer’s disease.Acta Neurol Scand DOI: 10.1111/j.1600-0404.2009.01230.x.© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard.Objective [ndash] 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 [ndash] To investigate the TNF[alpha][ndash]308, IL-6 [ndash]174 and IL-10 [ndash]1082 gene polymorphisms as susceptibility factors for AD.Methods [ndash] We analyzed genotype and allele distributions of these polymorphisms in 101 sporadic AD patients and 138 healthy controls.Results [ndash] Heterozygotes (AG) or combined genotype (AG+AA) for IL-10 [ndash]1082 were associated with approximately two-fold increase in the risk of AD. Carriers of A alleles of both TNF[alpha][ndash]308 and IL-10 [ndash]1082 had 6.5 times higher risk for AD in comparison with non-carriers. Concomitant presence of both mutant TNF[alpha][ndash]308 A and IL-6 [ndash]174 C alleles raised three-fold the AD risk, whereas there was no notable risk for AD afflicted by IL-6 [ndash]174 polymorphism alone.Conclusion [ndash] Our results suggest that TNF[alpha] and IL-10 promoter polymorphism might be a risk factor for AD. The combined effects of TNF[alpha][ndash]308, IL-6 [ndash]174 and IL-10 [ndash]1082 variant alleles may be more decisive to induce functional differences and modify the risk for AD.
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