Divalent cation transport and susceptibility to infectious and autoimmune disease: continuation of the Ity/Lsh/Bcg/Nramp1/Slc11a1 gene story

Blackwell, Jenefer M.; Searle, Susana; Mohamed, Hiba S.; White, Jacqueline K.

doi:10.1016/s0165-2478(02)00231-6

Cited by 144 publications

(117 citation statements)

References 46 publications

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“…Previous studies of inflammatory and autoimmune diseases (reviewed in Blackwell et al 18 ) and the clinical and immune response phenotypes associated with SA (reviewed 1 ) provided a priori evidence that allele 3 at the (GT) n the functional repeat polymorphism in the promoter region of SLC11A1 would be associated with SA. Data presented here provide evidence to support this prediction, both when SA patients were compared to healthy controls and to TB patients, in this Polish population.…”

Section: Discussionmentioning

confidence: 99%

“…Mycobacteria have also been implicated in triggering 13 -16 or protecting individuals from 15 -17 autoimmune disease. Polymorphic alleles at SLC11A1 have previously been associated with susceptibility to both these putative infectious agents and to these autoimmune disorders (reviewed in Blackwell et al 18 ). SLC11A1 encodes the natural resistance associated macrophage protein 1 that regulates divalent cation homeostasis in macrophages and has many pleiotropic effects on macrophage activation.…”

Section: Introductionmentioning

confidence: 99%

“…SLC11A1 encodes the natural resistance associated macrophage protein 1 that regulates divalent cation homeostasis in macrophages and has many pleiotropic effects on macrophage activation. 18 It is also known to be involved in determining Th1 versus Th2 bias in immune response to infection or specific antigens. In humans, no functional variants across the coding region of the gene have been identified, but a functional (GT) n repeat polymorphism has been identified 19 and characterized.…”

Section: Introductionmentioning

confidence: 99%

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Association between SLC11A1 (formerly NRAMP1) and the risk of sarcoidosis in Poland

Dubaniewicz

Jamieson

Dubaniewicz-Wybieralska

et al. 2005

Eur J Hum Genet

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Sarcoidosis (SA) is a systemic granulomatous disorder of unknown etiology characterized by T helper 1-type inflammatory responses at sites of disease with signs of B cell hyperactivity. Like rheumatoid arthritis and diabetes, an infectious etiology has frequently been postulated but no single infectious trigger definitively identified. Polymorphic alleles at SLC11A1 have previously been associated with susceptibility to both the putative infectious agents and to these autoimmune disorders. We therefore investigated its candidacy as a genetic determinant of SA in Poland in an association-based study comparing 86 SA patients with 85 tuberculosis (TB) patients and 93 control subjects. The functional promoter (GT) n polymorphism and four of 10 other single nucleotide or insertion/deletion polymorphisms genotyped across SLC11A1 were informative in our sample. Consistent with previous autoimmune disease studies, allele 3 at the functional (GT) n promoter region repeat polymorphism was significantly associated with SA when compared with healthy controls (odds ratio 1.68; 95% CI: 1.01-2.81; P ¼ 0.04) or with TB patients (odds ratio 1.69; 95% CI: 1.042-0.78; P ¼ 0.03).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association between SLC11A1 (formerly NRAMP1) and the risk of sarcoidosis in Poland

Dubaniewicz

Jamieson

Dubaniewicz-Wybieralska

et al. 2005

Eur J Hum Genet

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“…Nramp1 (Slc11a1), also known as Natural Resistance Associated Macrophage Protein 1 encodes a divalent cation transporter expressed in lysosomes, and phagosomes that plays a role in iron transport, redox homeostasis and the innate immune response (Blackwell et al, 2003;Canonne-Hergaux et al, 1999). Nramp1 functions as a pH dependent antiporter, and plays a role in phagosomal acidification (Hackam et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Altered expression of the iron transporter Nramp1 (Slc11a1) during fetal development of the retinal pigment epithelium in microphthalmia-associated transcription factor Mitfmi and Mitfvitiligo mouse mutants

Waes

Smith

Waes

et al. 2008

Experimental Eye Research

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Microphthalmia-associated Transcription Factor (Mitf) is expressed in neural crest cell-derived melanocytes, and in the retinal pigment epithelium (RPE) during ocular development. Mutations in Mitf are associated with auditory/visual/pigmentary syndromes in humans. Mitf mi/mi mouse mutants lack pigmentation, and are microphthalmic, while Mitf vit/vit mouse mutants display abnormal RPE pigmentation, and progressive retinal degeneration. Microarray analysis was used to identify novel downstream gene targets/pathways in the RPE that are altered by mutations in the transcription factor Mitf. Using the Affymetrix platform, gene expression profiles were generated using the eyes of E13.5 mouse fetuses that were wildtype, heterozygous, or homozygous for the Mitf mi mutation. In a separate experiment, eyes from E13.5 mouse fetuses homozygous for the Mitf vit mutation were compared to eyes from the C57BL/6 control background strain. Statistical analyses were performed using Robust Multiarray Average, mixed-effects ANOVA and random-variance t-tests. Altered expression of genes involved in pigment formation, melanosome biogenesis/transport, and redox homeostasis were observed. 12 genes were commonly mis-regulated in the eyes of both Mitf mutants: 10 of these genes were downregulated in both mutants relative to controls, while 2 of the genes (Nramp1 (Slc11a1) and epoxide hydrolase) were downregulated in Mitf mi/mi mutants, and conversely, upregulated in Mitf vit/vit mutants. Quantitative RT-PCR and immunohistochemistry were used to confirm altered gene/protein expression. RPE expression of the Fe +2 iron transporter Nramp1 (Slc11a1) has not previously been reported. Fe +2 is an important co-factor utilized by the iron-dependent isomerohydrolase RPE65 in the retinoid visual cycle. However, excess accumulation of Fe +2 in the RPE has recently been associated with oxidative damage and age-related macular degeneration. Abnormal pigmentation and increased activity of Slc11a1 in the RPE of Mitf vit mice may contribute to the pathology and progressive retinal degeneration observed in these mutants.

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“…A third study from our laboratory utilized previous findings indicating association between the solute carrier family 11 member 1 gene ( SLC11A1 ) and susceptibility to intracellular bacterial infections in other species of animals 23, 24, 25, 26. The SLC11A1 gene encodes a protein relevant to innate immune responses to intracellular bacteria 27, 28.…”

Section: Candidate Genesmentioning

confidence: 99%

Genetic Susceptibility to Rhodococcus equi

McQueen

Dindot

2015

Veterinary Internal Medicne

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Rhodococcus equi pneumonia is a major cause of morbidity and mortality in neonatal foals. Much effort has been made to identify preventative measures and new treatments for R. equi with limited success. With a growing focus in the medical community on understanding the genetic basis of disease susceptibility, investigators have begun to evaluate the interaction of the genetics of the foal with R. equi. This review describes past efforts to understand the genetic basis underlying R. equi susceptibility and tolerance. It also highlights the genetic technology available to study horses and describes the use of this technology in investigating R. equi. This review provides readers with a foundational understanding of candidate gene approaches, single nucleotide polymorphism‐based, and copy number variant‐based genome‐wide association studies, and next generation sequencing (both DNA and RNA).

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Divalent cation transport and susceptibility to infectious and autoimmune disease: continuation of the Ity/Lsh/Bcg/Nramp1/Slc11a1 gene story

Cited by 144 publications

References 46 publications

Association between SLC11A1 (formerly NRAMP1) and the risk of sarcoidosis in Poland

Association between SLC11A1 (formerly NRAMP1) and the risk of sarcoidosis in Poland

Altered expression of the iron transporter Nramp1 (Slc11a1) during fetal development of the retinal pigment epithelium in microphthalmia-associated transcription factor Mitfmi and Mitfvitiligo mouse mutants

Genetic Susceptibility to Rhodococcus equi

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