Pharmacogenetic analysis of the effects of polymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic on cognition in mild to moderate Alzheimer's disease; a randomized, double-blind, placebo-controlled study

BMC Med Genet. 2011 Oct 12:12:137. doi: 10.1186/1471-2350-12-137.

Abstract

Background: To examine the effect of genetic variation in APOE, IDE and IL1B on the response to induced ketosis in the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) in subjects with mild to moderate Alzheimer's disease (AD).

Methods: Genotype effects on ADAS-Cog scores from a randomized, double-blind, placebo-controlled study in mild to moderate AD were examined by an overall two way analysis of variance. In addition, interactions with the carriage status of the epsilon 4 allele of the APOE gene (APOE4) were examined.

Results: Significant differences in response to induced ketosis were found among non-carriers of putative gain-of-function polymorphisms in rs1143627 and rs16944 in the IL1B gene and among variants of the polymorphism rs2251101 in the IDE gene. Significant differences were found among non-carriers of the APOE4 gene, with notable improvement among the E3/E3 genotype group.

Conclusions: Variants in APOE, IL1B and IDE may influence the cognitive response to induced ketosis in patients with mild to moderate AD.

Trial registration: This trial was registered with ClinicalTrials.gov, registry number NCT00142805.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Apolipoprotein E3 / genetics*
  • Apolipoprotein E4 / genetics*
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / genetics
  • Double-Blind Method
  • Female
  • Humans
  • Insulysin / genetics*
  • Interleukin-1beta / genetics*
  • Ketone Bodies / therapeutic use*
  • Male
  • Polymorphism, Genetic
  • Severity of Illness Index

Substances

  • Apolipoprotein E3
  • Apolipoprotein E4
  • Interleukin-1beta
  • Ketone Bodies
  • Insulysin

Associated data

  • ClinicalTrials.gov/NCT00142805