The interleukin-6 gene -572C/G promoter polymorphism modifies Alzheimer's risk in APOE epsilon 4 carriers

Inflammatory response is involved in the etiopathology of Alzheimer's disease (AD). Interleukin-6 (IL-6), a pleiotropic inflammatory cytokine, was reported to be associated with both increased A beta aggregation and the appearance of hyperphosphorylated tau in AD brain. To explore the association of genetic variants in the promoter of IL-6 gene with sporadic AD (SAD), a case-control study was conducted in a North Chinese Han population. A systematic screening of IL-6 promoter was performed using direct sequencing and two polymorphisms were obtained including -572C/G (rs1800796) and -384A/T (rs7802308). Definitive genotyping of these markers and apolipoprotein E (APOE) polymorphism were surveyed in 341 SAD patients and 421 controls. The results revealed no significant differences in the distributions of alleles or genotypes between SAD and control groups. However, there was an interaction between -572C/G and APOE genotypes (P=0.016) using logistic analysis. In the subjects with APOE epsilon 4, there were significant differences in the allele (P=0.004) and genotype (P=0.004) distributions of -572C/G polymorphism between SAD and control groups. The -572CC genotype increased risk for AD by 3.301-fold (Wald=11.093, adjust OR=3.301, 95% CI=1.635-6.665, P=0.001) compared to CG+GG genotype. The present results suggest the -572 polymorphism could modify the risk for SAD in APOE epsilon 4 carriers.