Regulation of interleukin 6 by a polymorphic CpG within the frontal cortex in Alzheimer's disease

Abstract

The cytokine interleukin 6 (IL-6) has been linked to the pathogenesis of Alzheimer's disease (AD). This is the first study to investigate the genetic and epigenetic interactions in the control of IL-6 in human brain and its relation to AD neuropathology in prefrontal cortex tissues from AD and controls genotyped for the SNP -174 C/G rs1800795, a polymorphic CpG in which the G allele creates a CpG site. Within CC homozygotes there were significantly higher brain levels of IL-6 protein compared to G allele carriers. The C allele that resulted in an absence of methylation at a CpG was also associated with significant changes in methylation at neighboring CpGs. Furthermore, there were significant differences in methylation between CC and CG/GG at CpG sites in the AD and control groups. That DNA methylation was altered in the brains by the presence of rs1800795, which further correlated with protein levels suggests the presence of a polymorphic CpG and genetic-epigenetic interactions in the regulation of IL-6 in the prefrontal cortex within AD brains.

Keywords: Alzheimer’s disease; DNA methylation; Epigenetic; Interleukin-6; Neuroinflammation; Prefrontal cortex.