ArticleJournal of medical genetics1999
Evidence for a functional repeat polymorphism in the promoter of the human NRAMP1 gene that correlates with autoimmune versus infectious disease susceptibility.
Article in Journal of medical genetics, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 223 citations in OpenAlex.
- Genetic variants of SLC11A1 are associated with both autoimmune and infectious diseases: systematic review and meta-analysis.Genes and immunity · 2015Pooled it
- The 2SP Site Mutation in the Bovine Natural Resistance-Associated Macrophage 1 Promoter Exhibits Antituberculosis Potential.International journal of molecular sciences · 2025Article
- Polymorphisms in Immune Genes and Their Association with Tuberculosis Susceptibility: An Analysis of the African Population.The application of clinical genetics · 2024Review
- Bioinformatics pipeline to guide post-GWAS studies in Alzheimer's: A new catalogue of disease candidate short structural variants.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- SLC11A1 genetic variation and low expression may cause immune response impairment in TB patients.Genes and immunity · 2022Article
- STRs: Ancient Architectures of the Genome beyond the Sequence.Journal of molecular neuroscience : MN · 2021Review
- Is the Prevalence ofAnimals : an open access journal from MDPI · 2021Article
- Solute carrier transporters: the metabolic gatekeepers of immune cells.Acta pharmaceutica Sinica. B · 2020Review
- Analysis of Genetic Variation in the BovineFrontiers in microbiology · 2020Article
- The C-terminal D/E-rich domain of MBD3 is a putative Z-DNA mimic that competes for Zα DNA-binding activity.Nucleic acids research · 2018Article
- Toward deciphering the mechanistic role of variations in the Rep1 repeat site in the transcription regulation of SNCA gene.Neurogenetics · 2018Article
- The effects of the TOMM40 poly-T alleles on Alzheimer's disease phenotypes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2018Review
- Genetic variations at the human growth hormone receptor (GHR) gene locus are associated with idiopathic short stature.Journal of cellular and molecular medicine · 2017Article
- Functional Mechanisms of Microsatellite DNA in Eukaryotic Genomes.Genome biology and evolution · 2017Review
- Structural variants in SNCA gene and the implication to synucleinopathies.Current opinion in genetics & development · 2017Review
- Article
- Towards precision medicine in Alzheimer's disease: deciphering genetic data to establish informative biomarkers.Expert review of precision medicine and drug development · 2017Article
- APOE ε4-TOMM40 '523 haplotypes and the risk of Alzheimer's disease in older Caucasian and African Americans.PloS one · 2017Article
- The SSV Evaluation System: A Tool to Prioritize Short Structural Variants for Studies of Possible Regulatory and Causal Variants.Human mutation · 2016Article
- Positive selection in the SLC11A1 gene in the family Equidae.Immunogenetics · 2016Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
A polymorphism in the promoter of human NRAMP1 encodes a Z-DNA forming dinucleotide repeat with four alleles: (1) t(gt)5ac(gt)5ac(gt)11g; (2) t(gt)5ac(gt)5 ac(gt)10g; (3) t(gt)5ac(gt) ac(gt)9g; and (4) t(gt)5ac(gt)9g. Alleles 1 and 4 are rare (gene frequencies approximately 0.001); alleles 2 and 3 occur at gene frequencies approximately 0.20-0.25 and approximately 0.75-0.80, respectively. Here, luciferase reporter gene constructs are used to show that the four alleles differ in their ability to drive gene expression. In the absence of exogenous stimuli, alleles 1, 2, and 4 are poor promoters; allele 3 drives high expression, indicating that the repeat itself has endogenous enhancer activity. All four alleles show a similar percentage enhancement of reporter gene expression in the presence of interferon-gamma, consistent with the multiple interferon-gamma response elements both 5' and 3' of the Z-DNA forming repeat. However, while the addition of bacterial lipopolysaccharide (LPS) has no effect on alleles 1 and 4, it causes significant reduction in expression driven by allele 2 and enhances expression driven by allele 3, suggesting that the juxtaposition of LPS related response elements (NFkappaB, AP-1, NF-IL6) may be differentially affected by the two commonly occurring alleles. These results are consistent with the hypothesis that chronic hyperactivation of macrophages associated with allele 3 is functionally linked to autoimmune disease susceptibility, while the poor level of NRAMP1 expression promoted by allele 2 contributes to infectious disease susceptibility. Conversely, allele 3 protects against infectious disease and allele 2 against autoimmune disease. Hence, alleles that are detrimental in relation to autoimmune disease susceptibility may be maintained in the population because they improve survival to reproductive age following infectious disease challenge.
Indexed as
Identifiers
10227396PMC1734346W2140656310What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.