Association between an interleukin-6 promoter and 3 ' flanking region haplotype and reduced Alzheimer's disease risk in a German population

Several studies have demonstrated that interleukin-6 (IL-6) is involved in the pathogenesis of Alzheimer's disease (AD). We previously reported on an association between the C allele of a variable number of tandem repeat poly morphism in the 3' flanking region of IL-6 gene (IL-6vntr) and delayed init ial onset and reduced AD risk. A novel G/C polymorphism at position -174 in the IL-6 gene promoter (IL-6prom) has recently been identified and appears to influence the regulation of IL-6 expression. We examined this functiona l polymorphism in 102 AD patients and two control groups of 191 healthy sub jects and 160 depressed patients. There was no evidence for an allelic asso ciation between IL-6prom polymorphism and earlier age of onset or risk of A D. However, haplotype analysis showed a strong linkage disequilibrium betwe en IL-6vntr and IL-6prom and demonstrated an interaction between IL-6vntr a nd IL-6prom which modifies AD risk. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.