van Oijen Marieke, Arp Pascal P, de Jong Frank Jan, Hofman Albert, Koudstaal Peter J, Uitterlinden Andre G, Breteler Monique M B
Department of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
Neurosci Lett. 2006 Jul 10;402(1-2):113-7. doi: 10.1016/j.neulet.2006.03.050. Epub 2006 Apr 25.
Inflammatory mechanisms are involved in the pathogenesis of dementia. Inflammatory cytokines, including interleukin-6 (IL-6) and transforming growth factor beta1 (TGFbeta1), have been found in association with Alzheimer pathology and there is evidence for direct involvement of these cytokines in formation of amyloid plaques. Polymorphisms in genes encoding for IL-6 and TGFbeta1 are associated with plasma levels of IL-6 and TGFbeta1. Studies examining the association between polymorphisms in these genes and dementia yielded conflicting results. The purpose of this study was to examine the association between genetic variance in IL-6 and TGFbeta1 and risk of dementia. We examined this association in the Rotterdam Study, a prospective population-based cohort study in the elderly. Polymorphisms in the IL-6 (-174G>C) and TGFbeta1 gene (-800G>A, -509C>T, +10T>C, +25G>C and 263C>T) were genotyped and haplotypes of the TGFbeta1 gene were constructed. In a random subset IL-6 plasma levels were measured. During follow-up (mean 9.2 years), 743 dementia cases were identified. We estimated the association between individual polymorphisms and haplotypes with dementia with Cox' proportional hazard models. No association was found between the -174G>C polymorphism in the IL-6 gene and risk of dementia. No association was found between polymorphisms and constructed haplotypes in the TGFbeta1 gene and risk of dementia or Alzheimer's disease. No association was found between IL-6 genotype and IL-6 plasma levels in the random subset. Associations did not differ across APOE genotypes. Our findings do not suggest involvement of genetic variance in IL-6 and TGFbeta1 in the development of dementia.
炎症机制参与痴呆症的发病过程。已发现包括白细胞介素 -6（IL -6）和转化生长因子β1（TGFβ1）在内的炎性细胞因子与阿尔茨海默病病理相关，并且有证据表明这些细胞因子直接参与淀粉样斑块的形成。编码IL -6和TGFβ1的基因多态性与IL -6和TGFβ1的血浆水平相关。研究这些基因多态性与痴呆症之间关联的结果相互矛盾。本研究的目的是检验IL -6和TGFβ1的基因变异与痴呆症风险之间的关联。我们在鹿特丹研究中检验了这种关联，该研究是一项针对老年人的基于人群的前瞻性队列研究。对IL -6（-174G>C）和TGFβ1基因（-800G>A、-509C>T、+10T>C、+25G>C和263C>T）的多态性进行基因分型，并构建TGFβ1基因的单倍型。在一个随机子集中测量了IL -6血浆水平。在随访期间（平均9.2年），共识别出743例痴呆症病例。我们用Cox比例风险模型估计了个体多态性和单倍型与痴呆症之间的关联。未发现IL -6基因中的-174G>C多态性与痴呆症风险之间存在关联。未发现TGFβ1基因中的多态性和构建的单倍型与痴呆症或阿尔茨海默病风险之间存在关联。在随机子集中未发现IL -6基因型与IL -6血浆水平之间存在关联。不同APOE基因型之间的关联无差异。我们的研究结果并未表明IL -6和TGFβ1的基因变异参与痴呆症的发生发展。
