ε3/4 genotype of the apolipoprotein E is associated with higher risk of Alzheimer's disease in patients with type 2 diabetes mellitus

Gene. 2019 Jun 30:703:65-70. doi: 10.1016/j.gene.2019.03.024. Epub 2019 Mar 16.

Abstract

As a progressive and chronic disease, type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia with rising prevalence worldwide. The ε4 allele of the apolipoprotein E (ApoE) gene may be risk factor of severe peripheral neuropathy in T2DM patients. The association of ApoE polymorphism and Alzheimer's disease (AD) in T2DM patients remains largely unknown. Totally 156 T2DM patients with AD and 145 T2DM patients were included. The genotypes and allele frequency of ApoE were analyzed to explore the role of ApoE in AD in T2DM patients. The levels of total cholesterol (TC), triglyeride (TG), low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C) were detected to further investigate mechanism of ApoE. Genotype frequency ratio of genotype ε3/4, ε4/4 and allele ε4 among the T2DM patients with AD was obviously increased. The TC, TG and LDL-C levels of T2DM patients with ε3/4 genotype were higher than those with ε3/3 or ε2/3 genotype and the ε3/4 genotype, while the HDL-C level was on the contrary, suggesting that ε3/4 genotype elevated blood lipid levels in T2DM patients with AD, thus increasing the risk of AD in T2DM patients. ApoE polymorphism was associated with AD in T2DM patients. ApoE ε3/4 genotype was possibly to serve as a risk factor for AD in T2DM patients by enhancing the blood lipid levels.

Keywords: Alleles; Alzheimer's disease; Blood lipid levels; Gene polymorphism; Type 2 diabetes mellitus.

MeSH terms

  • Aged
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Apolipoproteins E / genetics*
  • Case-Control Studies
  • Cholesterol / metabolism
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Gene Frequency*
  • Genetic Association Studies / methods*
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Triglycerides / metabolism

Substances

  • ApoE protein, human
  • Apolipoproteins E
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Triglycerides
  • Cholesterol