Ma Suk Ling, Tang Nelson Leung Sang, Lam Linda Chiu Wa, Chiu Helen Fung Kum
Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Neurobiol Aging. 2005 Jul;26(7):1005-10. doi: 10.1016/j.neurobiolaging.2004.08.010. Epub 2004 Nov 23.
The importance of the role of inflammation has been suggested in the pathogenesis of Alzheimer's disease (AD). Interleukin-10 (IL-10) is an anti-inflammatory cytokine that may modulate the progression of the disease through the inhibition of the action of pro-inflammatory cytokines. In this study, three polymorphisms in the regulatory region of the IL-10 gene (-1082, -819 and -592) in 95 Chinese AD patients and 117 age-matched healthy Chinese subjects were investigated. We found that among the Chinese population, the A and C alleles at the -592 position are strongly linked to the T and C alleles at the -819 position, respectively. A strong association with AD was found for these two IL-10 polymorphisms, which are in complete linkage disequilibrium (-592C and -819C), and the odds ratio of AD is 4.03 (95% CI 1.23-13.23; p = 0.011). The functional significance of the IL-10 genotype was further supported by the significant association between plasma IL-10 concentrations and genotypes that were found in an independent sample of 160 healthy male volunteers. No interaction effect between the ApoE and IL-10 genotypes is found. Therefore, we concluded that the functional polymorphisms of the IL-10 gene act as a risk factor for AD.
炎症在阿尔茨海默病(AD)发病机制中的作用已受到关注。白细胞介素-10(IL-10)是一种抗炎细胞因子,可能通过抑制促炎细胞因子的作用来调节疾病进展。本研究对95例中国AD患者和117例年龄匹配的健康中国受试者的IL-10基因调控区的三个多态性位点(-1082、-819和-592)进行了研究。我们发现,在中国人群中,-592位点的A和C等位基因分别与-819位点的T和C等位基因紧密连锁。发现这两个处于完全连锁不平衡状态的IL-10多态性位点(-592C和-819C)与AD显著相关,AD的优势比为4.03(95%可信区间1.23 - 13.23;p = 0.011)。在160名健康男性志愿者的独立样本中发现血浆IL-10浓度与基因型之间存在显著关联,进一步支持了IL-10基因型的功能意义。未发现载脂蛋白E和IL-10基因型之间存在相互作用效应。因此,我们得出结论,IL-10基因的功能多态性是AD的一个危险因素。