The Role of NRAMP1/SLC11A1 Gene Variant D543N (1730G/A) in the Genetic Susceptibility to Develop Rheumatoid Arthritis in the Mexican Mestizo population

Niño-Moreno, Perla; Turrubiartes-Martínez, Edgar; Oceguera-Maldonado, Brenda; Baltazar-Benítez, Nubia; Negrete-González, Cindy; Oliva-Ramírez, Brenda; Baranda, Lourdes; González‐Amaro, Roberto

doi:10.24875/ric.17002152

Cited by 10 publications

(11 citation statements)

References 18 publications

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“…This twofold activity, which reflects polarization of MF phenotypes along the spectrum of M1 to M0 to M2 states, may contribute to the complexity in NRAMP1 activation, by analogy with different profiles of enhancer activation reported in Th1 vs. Th2 lymphocytes [20], even though mechanisms that differentiate Th cell subsets are not governed by combinations of lineage- and stimulus-dependent TFs such as those described in MFs [22,196]. In turn, complex regulation of NRAMP1 expression may partly explain how SNPs may be associated with susceptibility to infections and/or autoimmune diseases in different human populations [111,197,198,199,200]. …”

Section: Discussionmentioning

confidence: 99%

Developmental Control of NRAMP1 (SLC11A1) Expression in Professional Phagocytes

Cellier

2017

Biology

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NRAMP1 (SLC11A1) is a professional phagocyte membrane importer of divalent metals that contributes to iron recycling at homeostasis and to nutritional immunity against infection. Analyses of data generated by several consortia and additional studies were integrated to hypothesize mechanisms restricting NRAMP1 expression to mature phagocytes. Results from various epigenetic and transcriptomic approaches were collected for mesodermal and hematopoietic cell types and compiled for combined analysis with results of genetic studies associating single nucleotide polymorphisms (SNPs) with variations in NRAMP1 expression (eQTLs). Analyses establish that NRAMP1 is part of an autonomous topologically associated domain delimited by ubiquitous CCCTC-binding factor (CTCF) sites. NRAMP1 locus contains five regulatory regions: a predicted super-enhancer (S-E) key to phagocyte-specific expression; the proximal promoter; two intronic areas, including 3′ inhibitory elements that restrict expression during development; and a block of upstream sites possibly extending the S-E domain. Also the downstream region adjacent to the 3′ CTCF locus boundary may regulate expression during hematopoiesis. Mobilization of the locus 14 predicted transcriptional regulatory elements occurs in three steps, beginning with hematopoiesis; at the onset of myelopoiesis and through myelo-monocytic differentiation. Basal expression level in mature phagocytes is further influenced by genetic variation, tissue environment, and in response to infections that induce various epigenetic memories depending on microorganism nature. Constitutively associated transcription factors (TFs) include CCAAT enhancer binding protein beta (C/EBPb), purine rich DNA binding protein (PU.1), early growth response 2 (EGR2) and signal transducer and activator of transcription 1 (STAT1) while hypoxia-inducible factors (HIFs) and interferon regulatory factor 1 (IRF1) may stimulate iron acquisition in pro-inflammatory conditions. Mouse orthologous locus is generally conserved; chromatin patterns typify a de novo myelo-monocytic gene whose expression is tightly controlled by TFs Pu.1, C/ebps and Irf8; Irf3 and nuclear factor NF-kappa-B p 65 subunit (RelA) regulate expression in inflammatory conditions. Functional differences in the determinants identified at these orthologous loci imply that species-specific mechanisms control gene expression.

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Section: Discussionmentioning

confidence: 99%

Developmental Control of NRAMP1 (SLC11A1) Expression in Professional Phagocytes

Cellier

2017

Biology

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“…As shown in Figure , a total of 77 studies were identified by searching PubMed, CNKI, and Web of Science databases systemically and holistically. After excluding 17 repetitions, one data redundancy, 34 non‐RA, three non‐human, seven reviews, two meta‐analyses, four family genetics and two with data unavailable, five articles with available data matched the inclusion criteria and were enrolled in this meta‐analysis. However, one of these only had data on common homozygous carriers and the sum of heterozygote and rare homozygous carriers.…”

Section: Resultsmentioning

confidence: 99%

Association between rheumatoid arthritis and genetic variants of natural resistance‐associated macrophage protein 1 gene: A meta‐analysis

et al. 2018

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Aim:To evaluate the association between natural resistance-associated macrophage protein 1 (NRAMP1) polymorphisms and rheumatoid arthritis (RA).Method: All related studies were retrieved and screened from PubMed, CNKI and Web of Science. Pooled odds ratios (ORs) and 95% CIs were assessed for the strength of association between NRAMP1 and RA. Publication bias was measured by Begg's funnel plot and Egger's regression test. The robustness of this meta-analysis was detected by sensitivity analysis. Results:A total of five eligible publications were included in the present meta-analysis. The polled data showed no association between RA and NRAMP1 D543N and 1729 + 55del4 in the allele model. However, the relationship between RA and NRAMP1 INT4 was statistically significant (OR 1.65, 95% CI 1. 14-2.38). Genotypic analysis demonstrated that there were no associations between RA and NRAMP1 D543N, 1729 + 55del4 and INT4 in homozygous comparison (D543N: OR 0.97, 95% CI 0.15-6.09; 1729 + 55del4: OR 1.19, 95% CI 0.29-24.88; INT4: OR 3.18, 95% CI 0.62-16.26), dominant model (D543N: OR 1.04, 95% CI 0.61-61.78; 1729 + 55del4: OR 1.41, 95% CI 0.81-2.47; INT4: OR 1.22, 95% CI 0.72-2.06) and recessive model (D543N: OR 0.93, 95% CI 0.15-5.91; 1729 + 55del4: OR 0.99, 95% CI 0.26-3.86; INT4: OR 2.95, 95% CI 0.61-14.16). In heterozygous comparison, it no association was shown between RA and NRAMP1 D543N and INT4, excepting NRAMP1 1729 + 55del4 (OR 1.73, 95% CI 1.17-2.56). Further subgroup analysis indicated that NRAMP1 1729 + 55del4 and INT4 were related to RA in Asia and in the Hardy-Weinberg equilibrium group. There exists no publication bias in this meta-analysis. Conclusion: This meta-analysis indicated that NRAMP1 1729 + 55del4 and INT4 confer susceptibility to RA. K E Y W O R D S meta-analysis, NRAMP1, polymorphism, rheumatoid arthritis

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“…The variant was not only associated with TB but also was implicated in other diseases as well. The rs17235409 variant was among the list of host factors associated with susceptibility to leishmaniasis ( Ates et al, 2009 ) and rheumatoid arthritis ( Niño-Moreno et al, 2017 ; Braliou et al, 2019 ). Our analysis shows that rs17235409 might be a promotor/repression gene mutation, which could lead to significant phenotypic consequences.…”

Section: Discussionmentioning

confidence: 99%

Genetic Analysis of TB Susceptibility Variants in Ghana Reveals Candidate Protective Loci in SORBS2 and SCL11A1 Genes

et al. 2022

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Despite advancements made toward diagnostics, tuberculosis caused by Mycobacterium africanum (Maf) and Mycobacterium tuberculosis sensu stricto (Mtbss) remains a major public health issue. Human host factors are key players in tuberculosis (TB) outcomes and treatment. Research is required to probe the interplay between host and bacterial genomes. Here, we explored the association between selected human/host genomic variants and TB disease in Ghana. Paired host genotype datum and infecting bacterial isolate information were analyzed for associations using a multinomial logistic regression. Mycobacterium tuberculosis complex (MTBC) isolates were obtained from 191 TB patients and genotyped into different phylogenetic lineages by standard methods. Two hundred and thirty-five (235) nondisease participants were used as healthy controls. A selection of 29 SNPs from TB disease-associated genes with high frequency among African populations was assayed using a TaqMan® SNP Genotyping Assay and iPLEX Gold Sequenom Mass Genotyping Array. Using 26 high-quality SNPs across 326 case-control samples in an association analysis, we found a protective variant, rs955263, in the SORBS2 gene against both Maf and Mtb infections (PBH = 0.05; OR = 0.33; 95% CI = 0.32–0.34). A relatively uncommon variant, rs17235409 in the SLC11A1 gene was observed with an even stronger protective effect against Mtb infection (MAF = 0.06; PBH = 0.04; OR = 0.05; 95% CI = 0.04–0.05). These findings suggest SLC11A1 and SORBS2 as a potential protective gene of substantial interest for TB, which is an important pathogen in West Africa, and highlight the need for in-depth host-pathogen studies in West Africa.

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The Role of NRAMP1/SLC11A1 Gene Variant D543N (1730G/A) in the Genetic Susceptibility to Develop Rheumatoid Arthritis in the Mexican Mestizo population

Abstract: background:Rheumatoid arthritis is a chronic inflammatory disease whose cause has not been fully elucidated. However,

Cited by 10 publications

References 18 publications

Developmental Control of NRAMP1 (SLC11A1) Expression in Professional Phagocytes

Developmental Control of NRAMP1 (SLC11A1) Expression in Professional Phagocytes

Association between rheumatoid arthritis and genetic variants of natural resistance‐associated macrophage protein 1 gene: A meta‐analysis

Genetic Analysis of TB Susceptibility Variants in Ghana Reveals Candidate Protective Loci in SORBS2 and SCL11A1 Genes

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