FOXP3 and GATA3 Polymorphisms, Vitamin D3 and Multiple Sclerosis.

Concetta Scazzone,Giulia Bivona,Caterina Maria Gambino,Luisa Agnello,Paolo Ragonese,Marcello Ciaccio,Bruna Lo Sasso,Matteo Vidali,Giuseppina Candore,Anna Maria Ciaccio,Giuseppe Salemi,Rosaria Vincenza Giglio

doi:10.3390/brainsci11040415

Abstract

Background: Regulatory T cells (Tregs) alterations have been implicated in the pathogenesis of Multiple Sclerosis (MS). Recently, a crucial role of the X-Linked Forkhead Box P3 (FoxP3) for the development and the stability of Tregs has emerged, and FOXP3 gene polymorphisms have been associated with the susceptibility to autoimmune diseases. The expression of Foxp3 in Tregs is regulated by the transcription factor GATA binding-protein 3 (GATA3) and vitamin D3. The aim of this retrospective case-control study was to investigate the potential association between FOXP3 and GATA3 genetic variants, Vitamin D3, and MS risk. Methods: We analyzed two polymorphisms in the FOXP3 gene (rs3761547 and rs3761548) and a polymorphism in the GATA3 gene (rs3824662) in 106 MS patients and 113 healthy controls. Serum 25(OH)D3 was also measured in all participants. Results: No statistically significant genotypic and allelic differences were found in the distribution of FOXP3 rs3761547 and rs3761548, or GATA3 rs3824662 in the MS patients, compared with controls. Patients that were homozygous for rs3761547 had lower 25(OH)D3 levels. Conclusions: Our findings did not show any association among FOXP3 and GATA3 SNPs, vitamin D3, and MS susceptibility.

Highlights

Multiple Sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS)
No significant statistical association was found by logistic regression between FOXP3 rs3761547 and rs3761548 as well as GATA binding-protein 3 (GATA3) rs3824662 genotypes and MS disease
No association was found between FOXP3 rs3761548 and rs3761547 or GATA3 rs3824662 genotypes on the age of disease onset (p ranging from 0.284 to 0.955), diseases duration (p ranging from 0.259 to 0.547) Expanded Disability Status Scale (EDSS) (p ranging from 0.631 to 0.985), Multiple Sclerosis Severity Score (MSSS) (p ranging from 0.601 to 0.680) and annualized relapse rate (ARR) (p ranging from 0.203 to 0.900)

Summary

Introduction

Multiple Sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS). Tregs have an essential role in controlling the immune system by several mechanisms, including regulation of antigen-presenting cells (APC) function, induction of tolerance, cytolysis, and expression of inhibitory cytokines [4]. Many polymorphisms in the gene codifying for Foxp have been associated with reduced levels of Foxp and impaired suppressive function of Treg cells, resulting in the development of autoimmune diseases [10]. A crucial role of the X-Linked Forkhead Box P3 (FoxP3) for the development and the stability of Tregs has emerged, and FOXP3 gene polymorphisms have been associated with the susceptibility to autoimmune diseases. The expression of Foxp in Tregs is regulated by the transcription factor GATA binding-protein 3 (GATA3) and vitamin D3 The aim of this retrospective case-control study was to investigate the potential association between FOXP3 and GATA3 genetic variants, Vitamin D3, and MS risk. Conclusions: Our findings did not show any association among FOXP3 and GATA3 SNPs, vitamin D3, and MS susceptibility

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