rs1143679
badMag 6.5This is a variant in the ITGAM gene that changes a arginine to an histidine.
Key Literature Trait Associations
Systemic Lupus Erythematosus
rs1143679 is a missense variant in ITGAM (integrin alpha-M, encoding CD11b — the complement receptor 3 subunit). The R77H change reduces both ITGAM expression and CD11b's ability to bind fibrinogen and vitronectin. CR3 helps phagocytes clear immune complexes; when impaired, complexes accumulate and trigger inflammation — a lupus hallmark. The A allele increases lupus risk by ~76%. Replicated in European, African, Hispanic, and Asian populations, making it one of the most robustly validated non-HLA lupus loci.
Lupus nephritis
Among SLE patients, carriers of the rs1143679 A allele have significantly elevated risk of developing lupus nephritis (kidney involvement). In European ancestry patients, the OR for renal disease versus unaffected controls was 2.15 (p=4.69×10⁻²²), and a meta-analysis confirmed OR 2.131 (95% CI 1.565–2.903, p=1.6×10⁻⁷) specifically for lupus nephritis in Europeans. Associations have been corroborated in Han Chinese and Brazilian populations. Mechanistically, the R77H variant impairs Mac-1's ability to suppress FcγRIIA on neutrophils, potentially driving immune complex-mediated glomerular injury.
Free cholesterol in small HDL
A large GWAS (n=450,015) identified rs1143679 as significantly associated with free cholesterol levels in small HDL particles (beta = −0.02 mmol/L, p=8×10⁻¹¹). This association is biologically plausible given ITGAM/Mac-1's role in complement-mediated lipid clearance and phagocytic uptake of lipoproteins by macrophages. The effect size is modest and the clinical significance of this HDL subfraction change is uncertain, but the large sample size and genome-wide significance make this a credible secondary association.
▶GWAS Catalog Trait Associations (2)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
GWAS Catalog Trait Associations (2)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
▶ClinVar annotation
▶Research that mentions this SNP (3)
▶Identification of an Association of TNFAIP3 Polymorphisms With Matrix Metalloproteinase Expression in Fibroblasts in an Integrative Study of Systemic Sclerosis–Associated Genetic and Environmental FactorsFunctionalN=183Peng Wei et al.(2016)· Arthritis & Rheumatology
This functional genetic study examined 183 fibroblast strains from systemic sclerosis (SSc) patients and controls to identify SNP-trait associations with extracellular matrix gene expression in response to silica stimulation. SNP rs58905141 in TNFAIP3 (6q23.3) was consistently associated with MMP3 and MMP1 dose-response expression with 3.6 to 12.7-fold changes, remaining genome-wide significant in meta-analysis across Caucasian, African American, and Hispanic cohorts. Two other SSc-associated loci, IL2RA and ITGAM, also showed significant associations with MMP expression in silica-stimulated fibroblasts.
▶European genetic ancestry is associated with a decreased risk of lupus nephritisAssociationN=1,906Ilana B. Richman et al.(2012)· Arthritis & Rheumatism
This cross-sectional study of 1906 SLE patients found that European genetic ancestry is protective against lupus nephritis development. A 10% increase in European ancestry was associated with a 15% reduction in renal disease risk (OR 0.85, 95% CI 0.82-0.87, p=1.9×10^-30), independent of socioeconomic status and candidate genes including IRF5 (rs4728142), BLK (rs2736340), STAT4 (rs3024912), and ITGAM (rs9937837).
▶Confirmation of an association between rs6822844 at the Il2–Il21 region and multiple autoimmune diseases: Evidence of a general susceptibility locusAssociationN=1,747Amit K. Maiti et al.(2010)· Arthritis & Rheumatism
This study confirmed association between rs6822844 in the IL2-IL21 region and multiple autoimmune diseases in non-European populations, with significant associations in Colombian samples for systemic lupus erythematosus (OR 0.50, P=0.008), type 1 diabetes (OR 0.43, P=0.014), rheumatoid arthritis (OR 0.61, P=0.019), and primary Sjögren's syndrome (OR 0.46, P=0.033). Meta-analysis of 23 populations showed highly significant overall association (P=2.61×10⁻²⁵, OR 0.73) and disease-specific associations with inflammatory bowel disease (P=3.48×10⁻¹², OR 0.74), rheumatoid arthritis (P=3.61×10⁻⁶, OR 0.77), type 1 diabetes (P=5.33×10⁻⁵, OR 0.61), and celiac disease (P=5.30×10⁻³, OR 0.72).
Gene information from NCBI Gene. Variant classifications from ClinVar.
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