Inflammatory mechanisms are involved in the pathogenesis of dementia. Inflammatory cytokines, including interleukin-6 (IL-6) and transforming growth factor β1 (TGFβ1), 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 TGFβ1 are associated with plasma levels of IL-6 and TGFβ1. 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 TGFβ1 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 TGFβ1 gene (-800G>A, -509C>T, +10T>C, +25G>C and 263C>T) were genotyped and haplotypes of the TGFβ1 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 TGFβ1 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 TGFβ1 in the development of dementia.

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Neuroscience Letters
Department of Neurology

van Oijen, M, Arp, P.P, de Jong, F.J, Hofman, A, Koudstaal, P.J, Uitterlinden, A.G, & Breteler, M.M.B. (2006). Polymorphisms in the interleukin 6 and transforming growth factor β1 gene and risk of dementia. The Rotterdam Study. Neuroscience Letters, 402(1-2), 113–117. doi:10.1016/j.neulet.2006.03.050