First Report of CR1 Polymorphisms and Soluble CR1 Levels Associated with Late Onset Alzheimer’s Disease (LOAD) in Latin America

The CR1 gene has been widely studied in Alzheimer’s disease (AD), since its first association with the disease in 2009. Even after 11 years of this discovery, the role of this gene in AD has not yet been fully elucidated and the association of its variants was not validated in Latin American populat...

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Veröffentlicht in:Journal of molecular neuroscience 2020-09, Vol.70 (9), p.1338-1344
Hauptverfasser: Kretzschmar, Gabriela Canalli, Antoniazzi, Angela Adriane Hanel, Oliveira, Luana Caroline, Nisihara, Renato Mitsunori, Petzl-Erler, Maria Luiza, de Souza, Ricardo Lehtonen R., Boldt, Angelica Beate Winter
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Sprache:eng
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Zusammenfassung:The CR1 gene has been widely studied in Alzheimer’s disease (AD), since its first association with the disease in 2009. Even after 11 years of this discovery, the role of this gene in AD has not yet been fully elucidated and the association of its variants was not validated in Latin American populations. We genotyped five CR1 single nucleotide polymorphisms (SNPs rs6656401, rs3849266, rs2274567, rs4844610, and rs12034383) in up to 162 AD patients and 137 controls through PCR-SSP and iPLEX MassARRAY Platform (Sequenom), and measured soluble CR1 (sCR1) levels in plasma of 40 AD patients and 39 controls with an enzyme-linked immunosorbent assay (ELISA). Homozygosity for haplotype rs3849266*C_rs2274567*A ( CA/CA genotype) was associated with susceptibility to AD (OR = 2.94, p  = 0.018). Patients presented higher sCR1 levels in plasma than controls ( p  = 0.038). Furthermore, patients that carry the rs2274567*G allele (p.1208Arg) presented higher sCR1 levels than A/A (p.1208His/His) homozygotes ( p  = 0.036). This is the first study to validate the association of CR1 polymorphisms with late-onset Alzheimer’s disease, as well as to evaluate sCR1 levels in a Latin American population. SNPs present in the regulatory and coding regions of this gene may be playing a key role in the observed association, probably by interfering in Aβ plaques clearance. Inhibition may be due to the increase in local sCR1 levels observed in patients, which may result from polymorphisms leading to larger isoforms of CR1 and/or structural alterations of the protein that makes it less functional, as well as increased vesiculation of the molecules.
ISSN:0895-8696
1559-1166
DOI:10.1007/s12031-020-01547-2