Association of immunity-related gene SNPs with Alzheimer's disease

Exp Biol Med (Maywood). 2024 Nov 22:249:10303. doi: 10.3389/ebm.2024.10303. eCollection 2024.

Abstract

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by progressive cognitive decline. Genetic factors have been implicated in disease susceptibility as its etiology remains multifactorial. The CD33 and the HLA-DRB1 genes, involved in immune responses, have emerged as potential candidates influencing AD risk. In this study, 644 Lebanese individuals, including 127 AD patients and 250 controls, were genotyped, by KASP assay, for six SNPs selected from the largest GWAS study in 2021. Logistic regression analysis assessed the association between SNP genotypes and AD risk, adjusting for potential confounders. Among the six SNPs analyzed, rs1846190G>A in HLA-DRB1 and rs1354106T>G in CD33 showed significant associations with AD risk in the Lebanese population (p < 0.05). Carriers of the AG and AA genotypes of rs1846190 in HLA-DRB1 exhibited a protective effect against AD (AG: OR = 0.042, p = 0.026; AA: OR = 0.052, p = 0.031). The GT genotype of rs1354106T>G in CD33 was also associated with reduced risk (OR = 0.173, p = 0.005). Following Bonferroni correction, a significant correlation of rs1354106T > G with AD risk was established. Our results might highlight the complex interplay between genetic and immunological factors contributing to the development of the disease.

Keywords: Alzheimer’s disease; CD33; Lebanese population; immunity genes; rs1354106.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / immunology
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • HLA-DRB1 Chains* / genetics
  • Humans
  • Lebanon
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Sialic Acid Binding Ig-like Lectin 3* / genetics

Substances

  • Sialic Acid Binding Ig-like Lectin 3
  • HLA-DRB1 Chains
  • CD33 protein, human

Grants and funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.