Multiple Sclerosis: Shall We Target CD33?

Vasileios Siokas,Nikolaos Grigoriadis,Dimitrios P Bogdanos,Efthimios Dardiotis,Georgios M Hadjigeorgiou,Zisis Tsouris,Athina-Maria Aloizou,Christos Bakirtzis,Ioannis Liampas,Georgios Koutsis,Maria Anagnostouli

doi:10.3390/genes11111334

Abstract

Background: Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS). Myeloid lineage cells (microglia and macrophages) may participate in the pathogenic mechanisms leading to MS. CD33 is a transmembrane receptor, mainly expressed by myeloid lineage cells. CD33 rs3865444 is a promoter variant previously associated with Alzheimer’s disease, whose role in MS remains obscure. Objective: To assess the role of CD33 rs3865444 in MS risk. Methods: We genotyped 1396 patients with MS and 400 healthy controls for the presence of the CD33 rs3865444 variant. Odds ratios (ORs) with the respective 95% confidence intervals (CIs), were calculated with the SNPStats software, assuming five genetic models (co-dominant, dominant, recessive, over-dominant, and log-additive), with the G allele as the reference allele. The value of 0.05 was set as the threshold for statistical significance. Results: CD33 rs3865444 was associated with MS risk in the dominant (GG vs. GT + TT; OR (95% C.I.) = 0.79 (0.63–0.99), p = 0.041) and the over-dominant (GG + TT vs. GT; OR (95% C.I.) = 0.77 (0.61–0.97), p = 0.03) modes of inheritance. Given that the GG genotype was more frequent and the GT genotype was less frequent in MS patients compared to controls—while the observed frequency of the TT genotype did not differ between the two groups—the observed difference in MS risk may be stemming from either the GG (as a risk factor) or the GT (as a protective factor) genotype of CD33 rs3865444. Conclusions: Our preliminary results suggest a possible contribution of CD33 rs3865444 to MS. Therefore, larger multiethnic studies should be conducted, investigating the role of CD33 rs3865444 in MS.

Highlights

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS)
Our results showed that CD33 rs3865444 significantly influenced the risk of MS, as we observed a statistically significant association the variant and MS
CD33 rs3865444, as the GG one was more frequent, and the GT one was less frequent in MS patients compared to controls, while the observed frequency of the TT genotype did not differ between the two groups

Summary

Introduction

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS). Epidemiological data suggest that MS is commonest among women, peaks, incidence-wise, during the third decade ofGenes 2020, 11, 1334; doi:10.3390/genes11111334 www.mdpi.com/journal/genesGenes 2020, 11, 1334 life, and is the main cause of neurological disability during adulthood [1]. Regarding MS frequency, more than two million individuals suffer from MS throughout the world [2]. The genetic component of MS is indisputable [2]. The evidence for a genetic background of MS emerges from quite a few scientific sources. As a matter of fact, siblings of affected individuals with. Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS). Myeloid lineage cells (microglia and macrophages) may participate in the pathogenic mechanisms leading to MS. CD33 is a transmembrane receptor, mainly expressed by myeloid lineage cells. Rs3865444 is a promoter variant previously associated with Alzheimer’s disease, whose role in MS remains obscure. Objective: To assess the role of CD33 rs3865444 in MS risk.

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