FOXP3 and GATA3 Polymorphisms, Vitamin D3 and Multiple Sclerosis

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

doi:10.3390/brainsci11040415

Cited by 14 publications

(13 citation statements)

References 45 publications

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“…Vitamin D is notable for its wide-ranging biological functions, which involve, among other things, suppressing metastasis by inhibiting tumor progression, angiogenesis, and cell proliferation, or by apoptosis promotion in cancer cells [5,[16][17][18][19][20]. In lung cancer, specifically, in vivo and in vitro studies have been carried out, showing that 1,25-dihydroxycholecalciferol inhibits growth of lung cancerous cell lines and affects cell cycle regulation in squamous cell carcinoma models [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Impact of Genetic Polymorphisms on the Metabolic Pathway of Vitamin D and Survival in Non-Small Cell Lung Cancer

et al. 2021

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Vitamin D has been associated with risk, development, and progression of cancer. However, the genes involved in its metabolism are highly polymorphic, compromising its activity. The aim of this study is to evaluate the association between the gene polymorphisms involved in the metabolic pathway of vitamin D and survival in patients with non-small-cell lung cancer (NSCLC). The study was designed as an observational cohort which included 194 Caucasians patients from southern Spain with NSCLC. Real-time polymerase chain reaction was used to analyze the following polymorphisms: CYP27B1 rs4646536, rs3782130, and rs10877012; CYP24A1 rs6068816 and rs4809957; GC rs7041; CYP2R1 rs10741657; VDR rs1544410 (BsmI), rs11568820 (Cdx-2), rs2228570 (FokI), rs7975232 (ApaI), and rs731236 (TaqI). Progression-free survival (PFS) and overall survival were assessed. Cox regression showed that rs4646536 was associated with PFS in the general population (p = 0.0233) and in the non-resected NSCLC subgroup (p = 0.0233). In the resected NSCLC subgroup, rs11568820 was associated with OS (p = 0.0129) and rs7041 with PFS (p = 0.0447). In the non-resected NSCLC subgroup, rs6068816 was associated with PFS (p = 0.0048) and OS (p = 0.0089) and rs731236 and rs7975232 were associated with OS (p = 0.0005) and PFS (p = 0.0002), respectively. The other polymorphisms showed no effect on the results. The rs4646536, rs6068816, rs7041, rs11568820, rs731236, and rs7975232 polymorphisms are associated with survival in NSCLC and may have a substantial role as prognostic markers of the disease.

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Section: Introductionmentioning

confidence: 99%

Impact of Genetic Polymorphisms on the Metabolic Pathway of Vitamin D and Survival in Non-Small Cell Lung Cancer

et al. 2021

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“…IL1RAPL2 [148], GAD1 [149], EPHA5 [150], HTR1A [151], CADPS (calcium dependent secretion activator) [152], GABRG3 [153], LRFN5 [154] and CXCR1 [155] are expressed in autism spectrum disorders, but these genes might be novel target for AD. GAD2 [156], TAC3 [157], NCR1 [158], IL7R [159], GATA3 [160], FCRL3 [161] and IL18R1 [162] have been reported as most promising biomarkers for early diagnosis and prognosis prediction of multiple sclerosis, but these genes might be novel target for AD. FLT3 [163], CHRNB4 [164], PAK1 [165], CHRNB3 [166], GRIN2A [167], CHRNA6 [168], PENK (proenkephalin) [169], CHRNB4 [170], IGF2 [171], TLR9 [172] and CACNG5 [173] were revealed to serve an important role in Parkinson’s disease, but these genes might be novel target for AD.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analyses of significant genes, related pathways and candidate prognostic biomarkers in Alzheimer’s disease

Bm¹,

Cm²

2021

Preprint

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Alzheimers disease (AD) is one of the most common causes of dementia and frailty. This study aimed to use bioinformatics analysis to identify differentially expressed genes (DEGs) in AD. The Expression profiling by high throughput sequencing dataset GSE125583 was downloaded from the Gene Expression Omnibus (GEO) database and DEGs were identified. After assessment of Gene Ontology (GO) terms and pathway enrichment for DEGs, a protein protein interaction (PPI) network, module analysis, miRNA hub gene regulatory network construction and TF hub gene regulatory network were conducted via comprehensive target prediction and network analyses. Finally, we validated hub genes by receiver operating characteristic curve (ROC) and RT-PCR. In total, 956 DEGs were identified in the AD samples, including 479 up regulated genes and 477 down regulated genes. Functional enrichment analysis showed that these DEGs are mainly involved in the neuronal system, GPCR ligand binding, regulation of biological quality and cell communication. The hub genes of PAK1, ELAVL2, NSF, HTR2C, TERT, UBD, MKI67, HSPB1, PYHIN1 and TES might be associated with AD. The diagnostic value and expression levels of these hub genes in AD were further confirmed by ROC analysis and RT-PCR. In conclusion, we identified pathways and crucial candidate genes that affect the outcomes of patients with AD, and these genes might serve as potential therapeutic targets.

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“…The active form of vitamin D, 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), suppresses autoimmune diseases such as MS by reducing the production of proinflammatory cytokines such as IFN (interferon)-γ, IL (interleukin)-2, and IL-17, as well as enhancing the secretion of anti-inflammatory cytokines such as IL-4 and IL-10 [ 7 – 11 ]. A recent retrospective case–control study showed that the effect of vitamin D3 on MS susceptibility was not mediated by regulatory T cells (Tregs) [ 12 ]. Increased evidences suggest that decreased vitamin D levels is associated with an abnormal immune response in MS [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Mendelian randomization study updates the effect of 25-hydroxyvitamin D levels on the risk of multiple sclerosis

Wang

2022

J Transl Med

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Background Observational studies and previous Mendelian randomization (MR) studies have shown that genetically low 25-hydroxyvitamin D (25OHD) levels are associated with a high susceptibility to multiple sclerosis (MS). The present MR study aims to update the causal estimates for the effects of 25OHD levels on MS risk. Methods To date, the largest genome-wide association study (GWAS) for serum 25OHD (n = 401,460) and MS (14,498 MS cases and 24,091 controls) was used to assess the effect of serum 25OHD levels on MS. All participants were of European ancestry. The MR-egger_intercept test and Cochran’s Q statistic were used to determine the pleiotropy and the heterogeneity, respectively. MR-egger, weighted median, inverse variance weighted (multiplicative random effects), simple mode, and weighted mode methods were used to evaluate the causal association of serum 25OHD levels with MS. Finally, the effect of a single 25OHD SNP (single nucleotide polymorphism) on MS was used to test the SNP bias. Results One hundred and fifteen newly identified serum 25OHD genetic variants were extracted from a large-scale serum 25OHD GWAS dataset. The 20 most effective and independent 25OHD genetic instrumental variables were extracted from the MS GWAS summary statistics. Pleiotropy analysis suggested no significant pleiotropic variant among the 20 selected 25OHD genetic instrument variants in MS GWAS datasets. As serum levels of 25OHD based on genetic changes increased, the risk of MS decreased using MR-egger (Beta = − 0.940, p = 0.001; OR = 0.391), weighted median (Beta = − 0.835, p = 0.000; OR = 0.434), IVW (Beta = − 0.781, p = 0.000; OR = 0.458), simple mode (Beta = − 1.484, p = 0.016; OR = 0.227), and weighted mode (Beta = − 0.913, p = 0.000; OR = 0.401). Our results were robust, with no obvious bias based on investigating the single 25OHD SNP on MS. Conclusions Our analysis suggested a causal association between genetically increased serum 25OHD levels and reduced MS in the European population.

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FOXP3 and GATA3 Polymorphisms, Vitamin D3 and Multiple Sclerosis

Cited by 14 publications

References 45 publications

Impact of Genetic Polymorphisms on the Metabolic Pathway of Vitamin D and Survival in Non-Small Cell Lung Cancer

Impact of Genetic Polymorphisms on the Metabolic Pathway of Vitamin D and Survival in Non-Small Cell Lung Cancer

Bioinformatics analyses of significant genes, related pathways and candidate prognostic biomarkers in Alzheimer’s disease

Mendelian randomization study updates the effect of 25-hydroxyvitamin D levels on the risk of multiple sclerosis

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