ArticleHuman molecular genetics2014
Combined protein- and nucleic acid-level effects of rs1143679 (R77H), a lupus-predisposing variant within ITGAM.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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
20 citing papers in PubMed, 34 citations in OpenAlex.
- DIA proteomics of FFPE renal biopsies reveals two molecular subtypes of lupus nephritis and identifies APOL1 as candidate biomarker for stratification.Lupus science & medicine · 2026Article
- The 330 risk loci known for systemic lupus erythematosus (SLE): a review.Frontiers in lupus · 2024Article
- Extracellular Vesicle ITGAM and ITGB2 Mediate Severe Acute Pancreatitis-Related Acute Lung Injury.ACS nano · 2023Article
- Modeling of horizontal pleiotropy identifies possible causal gene expression in systemic lupus erythematosus.Frontiers in lupus · 2023Article
- Systemic lupus erythematosus as a genetic disease.Clinical immunology (Orlando, Fla.) · 2022Article
- Polygenic autoimmune disease risk alleles impacting B cell tolerance act in concert across shared molecular networks in mouse and in humans.Frontiers in immunology · 2022Review
- Polymorphism of the ITGAM gene (rs7193943) and bioelectric impedance analysis as potential predictors of cachexia in chronic heart failure.Scientific reports · 2021Article
- Polymorphism of The Regulatory Region of theJournal of clinical medicine · 2020Article
- Deep sequencing reveals a DAP1 regulatory haplotype that potentiates autoimmunity in systemic lupus erythematosus.Genome biology · 2020Article
- Identification of Key Genes and Pathways in Myeloma side population cells by Bioinformatics Analysis.International journal of medical sciences · 2020Article
- Mice expressing the variant rs1143679 allele of ITGAM (CD11b) show impaired DC-mediated T cell proliferation.Mammalian genome : official journal of the International Mammalian Genome Society · 2019Article
- The Post-GWAS Era: How to Validate the Contribution of Gene Variants in Lupus.Current rheumatology reports · 2019Review
- Article
- CD11b activation suppresses TLR-dependent inflammation and autoimmunity in systemic lupus erythematosus.The Journal of clinical investigation · 2017Article
- Confirmation of five novel susceptibility loci for systemic lupus erythematosus (SLE) and integrated network analysis of 82 SLE susceptibility loci.Human molecular genetics · 2017Article
- The complement receptor 3 (CD11b/CD18) agonist Leukadherin-1 suppresses human innate inflammatory signalling.Clinical and experimental immunology · 2016Article
- High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry.Nature genetics · 2016Article
- Advances in lupus genetics and epigenetics.Current opinion in rheumatology · 2014Review
- CD11c/CD18 Dominates Adhesion of Human Monocytes, Macrophages and Dendritic Cells over CD11b/CD18.PloS oneArticle
- Genetic analysis of the pathogenic molecular sub-phenotype interferon-alpha identifies multiple novel loci involved in systemic lupus erythematosus.Genes and immunityArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 7 institutions in 4 countries.
Funding
Abstract
Integrin alpha M (ITGAM; CD11b) is a component of the macrophage-1 antigen complex, which mediates leukocyte adhesion, migration and phagocytosis as part of the immune system. We previously identified a missense polymorphism, rs1143679 (R77H), strongly associated with systemic lupus erythematosus (SLE). However, the molecular mechanisms of this variant are incompletely understood. A meta-analysis of published and novel data on 28 439 individuals with European, African, Hispanic and Asian ancestries reinforces genetic association between rs1143679 and SLE [Pmeta = 3.60 × 10(-90), odds ratio (OR) = 1.76]. Since rs1143679 is in the most active region of chromatin regulation and transcription factor binding in ITGAM, we quantitated ITGAM RNA and surface protein levels in monocytes from patients with each rs1143679 genotype. We observed that transcript levels significantly decreased for the risk allele ('A') relative to the non-risk allele ('G'), in a dose-dependent fashion: ('AA' < 'AG' < 'GG'). CD11b protein levels in patients' monocytes were directly correlated with RNA levels. Strikingly, heterozygous individuals express much lower (average 10- to 15-fold reduction) amounts of the 'A' transcript than 'G' transcript. We found that the non-risk sequence surrounding rs1143679 exhibits transcriptional enhancer activity in vivo and binds to Ku70/80, NFKB1 and EBF1 in vitro, functions that are significantly reduced with the risk allele. Mutant CD11b protein shows significantly reduced binding to fibrinogen and vitronectin, relative to non-risk, both in purified protein and in cellular models. This two-pronged contribution (nucleic acid- and protein-level) of the rs1143679 risk allele to decreasing ITGAM activity provides insight into the molecular mechanisms of its potent association with SLE.
Indexed as
Identifiers
What 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.