Di Bona Danilo, Plaia Antonella, Vasto Sonya, Cavallone Luca, Lescai Francesco, Franceschi Claudio, Licastro Federico, Colonna-Romano Giuseppina, Lio Domenico, Candore Giuseppina, Caruso Calogero
Istituto di Biomedicina ed Immunologia Molecolare (IBIM), CNR, Palermo Università di Palermo, Italy.
Brain Res Rev. 2008 Nov;59(1):155-63. doi: 10.1016/j.brainresrev.2008.07.003. Epub 2008 Jul 21.
The pro-inflammatory cytokine interleukin(IL)-1beta is a main component in inflammatory pathways and is overexpressed in the brain of Alzheimer's disease (AD) patients. Several studies report associations between IL-1beta polymorphisms and AD, but findings from different studies are controversial. Our aim was to verify the correlation between the single nucleotide polymorphisms (SNPs) of the IL-1beta, at sites -511 and +3953, and AD by meta-analysis. Computerized bibliographic searches of PUBMED and AlzGene database (http://www.alzgene.org) were supplemented with manual searches of reference lists. There is evidence for association between IL-1beta +3953 SNP and AD, with an OR=1.60 (95% C.I.: 1.16-2.22; Z=2.83 p=0.005) for TT genotype. No significant difference in genotype distribution of the IL-1beta -511 SNP in AD was obtained, but high between-study heterogeneity was found. To reduce heterogeneity, subgroup analyses were performed using, as stratifying variables, characteristics of the population under study (age, gender, type of AD diagnosis, Mini Mental State Examination of the controls) and characteristics related to the study design (statistical power of individual studies). The frequency of the IL-1beta -511 TT genotype resulted significantly higher than other genotypes only when the Caucasian studies with the highest statistical power were included in the subgroup analysis (OR=1.32; 95% C.I.: 1.03-1.69; p=0.03), with no evidence of between-study heterogeneity. Our data support an association between the TT genotype of IL-1beta +3953 SNP and AD, and suggest a possible association of the -511 TT genotype. Unreplicability of the results seems to be due mainly to the lack of statistical power of the individual studies.
促炎细胞因子白细胞介素（IL）-1β是炎症通路的主要成分，在阿尔茨海默病（AD）患者的大脑中过度表达。多项研究报道了IL-1β基因多态性与AD之间的关联，但不同研究的结果存在争议。我们的目的是通过荟萃分析验证IL-1β基因位于-511和+3953位点的单核苷酸多态性（SNP）与AD之间的相关性。通过对PUBMED和AlzGene数据库（http://www.alzgene.org）进行计算机化文献检索，并辅以手动检索参考文献列表。有证据表明IL-1β +3953 SNP与AD之间存在关联，TT基因型的比值比（OR）=1.60（95%置信区间：1.16-2.22；Z=2.83，p=0.005）。AD患者中IL-1β -511 SNP的基因型分布无显著差异，但研究间异质性较高。为了降低异质性，使用所研究人群的特征（年龄、性别、AD诊断类型、对照组简易精神状态检查）和与研究设计相关的特征（个体研究的统计效能）作为分层变量进行亚组分析。仅当亚组分析纳入统计效能最高的白种人研究时，IL-1β -511 TT基因型的频率才显著高于其他基因型（OR=1.32；95%置信区间：1.03-1.69；p=0.03），且无研究间异质性的证据。我们的数据支持IL-1β +3953 SNP的TT基因型与AD之间的关联，并提示-511 TT基因型可能存在关联。结果的不可重复性似乎主要是由于个体研究缺乏统计效能。
