Influence of the apolipoprotein E epsilon4 allele on human embryonic development

Neurosci Lett. 2002 May 24;324(3):189-92. doi: 10.1016/s0304-3940(02)00198-2.


Human apolipoprotein E (apoE) exists in three major isoforms encoded by distinct alleles (APOE epsilon2, epsilon3 and epsilon4) and has important functions in nerve development and repair. Inheritance of the 4 allele is a major risk factor for the development of Alzheimer's disease. To investigate the role of APOE polymorphisms in embryonic development, we analyzed the APOE genotypes of 81 spontaneously aborted embryos and 110 adult controls using a solid-phase minisequencing technique. The epsilon4 allele was significantly less frequent in the spontaneous abortion group than in the control group (P=0.009), while the frequency of epsilon3 was significantly increased (P=0.005), suggesting that epsilon4 may have protective effects during embryogenesis. These protective effects might counterbalance the deleterious age-related effects of the epsilon4 allele in natural selection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoprotein E2
  • Apolipoprotein E3
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Apolipoproteins E / metabolism
  • DNA Mutational Analysis
  • Embryo, Mammalian / embryology*
  • Embryo, Mammalian / metabolism
  • Female
  • Fetus / embryology*
  • Fetus / metabolism
  • Gene Expression Regulation, Developmental / genetics*
  • Gene Frequency / genetics*
  • Genetic Testing
  • Genotype
  • Humans
  • Polymorphism, Genetic / genetics*
  • Pregnancy


  • Apolipoprotein E2
  • Apolipoprotein E3
  • Apolipoprotein E4
  • Apolipoproteins E