Genetic association of BIN1 and GAB2 in Alzheimer's disease: A meta-analysis and systematic review

Geriatr Gerontol Int. 2021 Feb;21(2):185-191. doi: 10.1111/ggi.14109. Epub 2020 Dec 16.

Abstract

Aim: Heredity plays an important role in the pathogenesis of Alzheimer's disease (AD) especially for single-nucleotide polymorphism (SNPs) of susceptible genes, which is one of the significant factors in the pathogenesis of AD. The SNPs of BIN1 rs744373, BIN1 rs7561528 and GAB2 rs2373115 are associated with AD in Asian and white people.

Methods: We included 34 studies with a total of 38 291 patients with AD and 55 538 controls of diverse races from four main databases. We used meta-analysis to obtain I2 -values and odds ratios of five genetic models in three SNPs. We carried out analysis of sensitivity, subgroup, publication bias and linkage disequilibrium test.

Results: The forest plots showed the odds ratio value of the three SNPs was >1 in white individuals, but not Asian individuals, in their genetic model. The funnel plot was symmetrical, and the D'-value was 0.986 between rs744373 and rs7561528.

Conclusions: BIN1 rs744373, BIN1 rs7561528 and GAB2 rs2373115 are pathogenicity sites for AD in white people, and also rs7561528 belongs to a risk site in Asian people. The rs7561528 and rs744373 SNPs have strong linkage disequilibrium in Chinese people. In addition, apolipoprotein E ε4 status promotes them to result in the pathogenesis of AD. Geriatr Gerontol Int 2021; 21: 185-191.

Keywords: Alzheimer's disease; GRB-associated binding protein 2; bridging integrator 1; linkage disequilibrium; meta-analysis.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Alzheimer Disease* / genetics
  • Genetic Predisposition to Disease
  • Humans
  • Nuclear Proteins / genetics
  • Polymorphism, Single Nucleotide
  • Tumor Suppressor Proteins / genetics
  • White People

Substances

  • Adaptor Proteins, Signal Transducing
  • BIN1 protein, human
  • GAB2 protein, human
  • Nuclear Proteins
  • Tumor Suppressor Proteins