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Diseases/Lupus/Genes/ITGAM

SLE gene evidence

ITGAM

Integrin subunit alpha M · CD11b

Evidence summaryRobust association with SLE across multiple ancestriesShared and ancestry-specific association signals

Overview

A myeloid immune-cell receptor

ITGAM is a well-established genetic risk gene for systemic lupus erythematosus.

ITGAM encodes CD11b, which combines with CD18 to form complement receptor 3 (CR3). Predominantly expressed on myeloid immune cells, CR3 contributes to leukocyte adhesion and migration, complement-mediated recognition, phagocytosis and inflammatory signalling.

Key findingTransancestral evidence supports a shared association involving rs1143679 alongside additional signals whose lead markers differ between populations.

Genetic association with SLE

Evidence across three ancestries

Association at ITGAM was observed in European, African American and Hispanic Amerindian participants. Odds ratios above one indicate increased susceptibility for the measured allele.

Population 01Shared missense signal
European ancestry

rs1143679

Missense variant

Risk allele: A
Odds ratio1.72
95% CI1.61–1.83
P-value2.78 × 10⁻⁶²

Risk-allele frequency0.180 cases · 0.108 controls

The strongest biologically plausible coding candidate among the leading European associations.

Regional context

The nearby intronic variant rs34572943 showed a similar effect and marked the same principal signal. Conditional evidence for rs72799341 suggests an additional association at the locus.

Population 02Cross-ancestry replication
African American ancestry

rs1143679

Missense variant

Risk allele: A
Odds ratio1.54
95% CI1.37–1.73
P-value1.62 × 10⁻¹³

Risk-allele frequency0.156 cases · 0.107 controls

The same missense variant associated with SLE in Europeans was strongly associated in African Americans.

Regional context

The shared risk allele and consistent direction of effect support an ancestry-independent component of the ITGAM association, although the estimated effect was smaller than in the European cohort.

Population 03Ancestry-specific lead marker
Hispanic Amerindian ancestry

rs13338069

Intronic variant

Risk allele: C
Odds ratio1.98
95% CI1.72–2.28
P-value1.94 × 10⁻²¹

Risk-allele frequency0.162 cases · 0.098 controls

The principal signal was represented by rs13338069 and the nearby intronic variant rs12928725.

Regional context

A second intronic marker, rs9926533, showed a protective association and retained evidence in regional stepwise analysis, supporting an additional association at this locus.

Current understanding

A robust locus with population-specific architecture

01

Shared association

rs1143679 is strongly associated in both European and African American populations, supporting a cross-ancestry risk component.

02

Local differences

In Hispanic Amerindian ancestry, the strongest markers are rs13338069 and rs12928725, with evidence for a second protective signal at rs9926533.

03

Causal interpretation

rs1143679 is compelling because it alters the CD11b protein sequence, but association evidence alone does not establish it as the sole causal variant.

Key reference

Evidence source