Vural P, Değirmencioğlu S, Parildar-Karpuzoğlu H, Doğru-Abbasoğlu S, Hanagasi H A, Karadağ B, Gürvit H, Emre M, Uysal M
Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Capa, 34093, Istanbul, Turkey.
Acta Neurol Scand. 2009 Dec;120(6):396-401. doi: 10.1111/j.1600-0404.2009.01230.x. Epub 2009 Sep 10.
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.
To investigate the TNFalpha-308, IL-6 -174 and IL-10 -1082 gene polymorphisms as susceptibility factors for AD.
We analyzed genotype and allele distributions of these polymorphisms in 101 sporadic AD patients and 138 healthy controls.
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.
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.
肿瘤坏死因子α（TNFα）、白细胞介素（IL）-6和IL-10细胞因子基因调控区的单核苷酸多态性被认为会影响阿尔茨海默病（AD）的发病风险，但结果相互矛盾。
研究TNFα -308、IL-6 -174和IL-10 -1082基因多态性作为AD的易感因素。
我们分析了101例散发性AD患者和138例健康对照者中这些多态性的基因型和等位基因分布。
IL-10 -1082的杂合子（AG）或联合基因型（AG + AA）与AD风险增加约两倍相关。TNFα -308和IL-10 -1082的A等位基因携带者患AD的风险是非携带者的6.5倍。突变型TNFα -308 A和IL-6 -174 C等位基因同时存在使AD风险增加三倍，而单独的IL-6 -174多态性对AD发病没有显著风险。
我们的结果表明，TNFα和IL-10启动子多态性可能是AD的一个风险因素。TNFα -308、IL-6 -174和IL-10 -1082变异等位基因的联合作用可能对诱导功能差异和改变AD风险更具决定性。
