Validating GWAS Variants from Microglial Genes Implicated in Alzheimer’s Disease
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Late-onset Alzheimer’s disease (LOAD) is a multifactorial neurodegenerative disorder that corresponds to most Alzheimer’s disease (AD) cases. Inflammation is frequently related to AD, whereas microglial cells are the major phagocytes in the brain and mediate the removal of Aβ peptides. Microglial cell dsyregulation might contribute to the formation of amyloid plaques, a hallmark of AD. Genome-wide association studies have reported genetic loci associated with the inflammatory pathway involved in AD. Among them, rs3865444 CD33, rs3764650 ABCA7, rs6656401 CR1, and rs610932 MS4A6A variants in microglial genes are associated with LOAD. These variants are proposed to participate in the clearance of Aβ peptides. However, their association with LOAD was not validated in all case-control studies. Thus, the present work aimed to assess the involvement of CD33 (rs3865444), ABCA7 (rs3764650), CR1 (rs6656401), and MS4A6A (rs610932) with LOAD in a sample from southeastern Brazil. The genotype frequencies were assessed in 79 AD patients and 145 healthy elders matched for sex and age. We found that rs3865444 CD33 acts as a protective factor against LOAD. These results support a role for the inflammatory pathway in LOAD.
KeywordsLoad Case-control study Microglial genes Polymorphisms
We appreciate the support of the researchers from the Núcleo de Genética Humana e Molecular – NGHM, Brazil. We thank the Instituto de Biociência, Universidade de São Paulo and Núcleo de Biotecnologia, Universidade Federal do Espírito Santo, Brazil for technical support. This study was financially supported by the Universidade Federal do Espírito Santo – UFES; Fundo de Amparo e Pesquisa do Espírito Santo – FAPES; Departamento de Ciência e Tecnologia do Ministério da Saúde - Decit; Secretaria de Ciência, Tecnologia e Insumos Estratégicos do Ministério da Saúde - SCTIE/MS; Fundo de Apoio à Ciência e Tecnologia do Município de Vitória - FACITEC; Ministério da Ciência, Tecnologia e Inovação - MCTI; Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPQ; Ministério da Educação – MEC and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES.
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Conflict of Interest
The authors declare that they have no conflict of interest.
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