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Article

CD33 rs2455069 SNP: Correlation with Alzheimer’s Disease and Hypothesis of Functional Role

by
Fabiana Tortora
1,†,
Antonella Rendina
1,†,
Antonella Angiolillo
2,
Alfonso Di Costanzo
2,
Francesco Aniello
3,
Aldo Donizetti
1,3,*,
Ferdinando Febbraio
1,‡ and
Emilia Vitale
1,*,‡
1
Institute of Biochemistry and Cell Biology, National Research Council (CNR), Via Pietro Castellino 111, 80131 Naples, Italy
2
Centre for Research and Training in Medicine of Aging, Department of Medicine and Health Science “V. Tiberio”, University of Molise, 86100 Campobasso, Italy
3
Department of Biology, University of Naples Federico II, 80126 Naples, Italy
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
These authors contributed equally to this work.
Int. J. Mol. Sci. 2022, 23(7), 3629; https://doi.org/10.3390/ijms23073629
Submission received: 25 February 2022 / Revised: 22 March 2022 / Accepted: 22 March 2022 / Published: 26 March 2022
(This article belongs to the Special Issue Genetics and Epigenetics in Complex Diseases)
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Abstract

The CD33 gene encodes for a member of the sialic-acid-binding immunoglobulin-type lectin (Siglec) family, and is one of the top-ranked Alzheimer’s disease (AD) risk genes identified by genome-wide association studies (GWAS). Many CD33 polymorphisms are associated with an increased risk of AD, but the function and potential mechanism of many CD33 single-nucleotide polymorphisms (SNPs) in promoting AD have yet to be elucidated. We recently identified the CD33 SNP rs2455069-A>G (R69G) in a familial form of dementia. Here, we demonstrate an association between the G allele of the rs2455069 gene variant and the presence of AD in a cohort of 195 patients from southern Italy. We carried out in silico analysis of the 3D structures of CD33 carrying the identified SNP to provide insights into its functional effect. Structural models of the CD33 variant carrying the R69G amino acid change were compared to the CD33 wild type, and used for the docking analysis using sialic acid as the ligand. Our analysis demonstrated that the CD33-R69G variant may bind sialic acid at additional binding sites compared to the wild type, thus potentially increasing its affinity/specificity for this molecule. Our results led to a new hypothesis of rs2455069-A>G SNP as a risk factor for AD, suggesting that a long-term cumulative effect of the CD33-R69G variant results from the binding of sialic acid, acting as an enhancer of the CD33 inhibitory effects on amyloid plaque degradation.
Keywords: CD33; Alzheimer’s disease; sialic acid; phagocytosis CD33; Alzheimer’s disease; sialic acid; phagocytosis

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MDPI and ACS Style

Tortora, F.; Rendina, A.; Angiolillo, A.; Di Costanzo, A.; Aniello, F.; Donizetti, A.; Febbraio, F.; Vitale, E. CD33 rs2455069 SNP: Correlation with Alzheimer’s Disease and Hypothesis of Functional Role. Int. J. Mol. Sci. 2022, 23, 3629. https://doi.org/10.3390/ijms23073629

AMA Style

Tortora F, Rendina A, Angiolillo A, Di Costanzo A, Aniello F, Donizetti A, Febbraio F, Vitale E. CD33 rs2455069 SNP: Correlation with Alzheimer’s Disease and Hypothesis of Functional Role. International Journal of Molecular Sciences. 2022; 23(7):3629. https://doi.org/10.3390/ijms23073629

Chicago/Turabian Style

Tortora, Fabiana, Antonella Rendina, Antonella Angiolillo, Alfonso Di Costanzo, Francesco Aniello, Aldo Donizetti, Ferdinando Febbraio, and Emilia Vitale. 2022. "CD33 rs2455069 SNP: Correlation with Alzheimer’s Disease and Hypothesis of Functional Role" International Journal of Molecular Sciences 23, no. 7: 3629. https://doi.org/10.3390/ijms23073629

APA Style

Tortora, F., Rendina, A., Angiolillo, A., Di Costanzo, A., Aniello, F., Donizetti, A., Febbraio, F., & Vitale, E. (2022). CD33 rs2455069 SNP: Correlation with Alzheimer’s Disease and Hypothesis of Functional Role. International Journal of Molecular Sciences, 23(7), 3629. https://doi.org/10.3390/ijms23073629

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