rs1800896 — IL10 -1082 A>G
Promoter variant affecting IL-10 production — the master anti-inflammatory cytokine that regulates immune response
Details
- Gene
- IL10
- Chromosome
- 1
- Risk allele
- G
- Consequence
- Regulatory
- Inheritance
- Codominant
- Clinical
- Risk Factor
- Evidence
- Strong
- Chip coverage
- v3 v4 v5
Population Frequency
Ancestry Frequencies
Related SNPs
Category
Immune & GutIL-10 Production — Your Anti-Inflammatory Thermostat
Interleukin-10 (IL-10) is the body's master anti-inflammatory cytokine, acting as a brake on immune responses to prevent excessive inflammation. The IL10 gene on chromosome 111 chromosome 1
Located at 1q31-32 produces this critical regulatory protein. The -1082 A>G polymorphism (rs1800896) sits in the promoter region of the gene, functioning as a dimmer switch that determines how much IL-10 your immune cells produce when inflammation begins.
The Mechanism
The -1082 position is part of a highly polymorphic promoter region that forms three predominant haplotypes (GCC, ACC, ATA) controlling IL-10 transcription .
The G allele at -1082 and haplotypes containing this allele have been associated with high IL-10 production, while the A allele and the ATA haplotype have been associated with low IL-10 production . The variant affects binding sites for transcription factors like Sp1, which regulate how actively the gene is transcribed into messenger RNA.
This isn't simply a "more is better" scenario. High IL-10 production (GG genotype) can suppress inflammatory responses effectively, but it can also dampen the immune system's ability to clear infections and may contribute to autoimmune disease through complex mechanisms involving B-cell activation and autoantibody production.
The Evidence
The functional consequences of this variant have been documented across multiple autoimmune and inflammatory conditions.
In ankylosing spondylitis, the IL10 -1082 G allele shows an odds ratio of 1.83, and AG/GG genotypes confer a 3-fold increased risk (OR 3.01, 95% CI 1.75-5.17) .
IL-10 serum levels were significantly higher in AS patients (2.38 pg/mL) compared to controls (1.72 pg/mL) .
In rheumatoid arthritis, North Indian studies found GG and AG genotypes associated with disease susceptibility (OR 2.87 and 1.55 respectively) .
The GG genotype shows higher prevalence in rheumatoid factor-negative RA patients, suggesting influence on autoantibody production .
The variant's role in inflammatory bowel disease22 inflammatory bowel disease
Crohn's disease and ulcerative colitis is particularly nuanced.
The IL10 rs1800896 variant allele (G) was associated with better biochemical remission in IBD patients on biologic therapy (OR 2.15, 95% CI 1.03-4.44), remaining significant after multivariate analysis (aOR 4.15, CI 1.49-11.56) . However, the AG genotype shows increased risk for both UC and CD in Mexican populations , highlighting the complexity of IL-10's role.
Systemic lupus erythematosus33 Systemic lupus erythematosus
SLE demonstrates similar complexity.
The GG genotype of -1082 polymorphism was associated with increased SLE risk (OR 2.65, 95% CI 1.21-5.82) .
IL10 plasma levels were overexpressed in CC genotype carriers of -592 SNP and decreased in AA genotype carriers of -1082 .
In sickle cell disease, the GG genotype was associated with significantly higher IL-10 levels (22.12 pg/ml) compared to AG genotype (13.94 pg/ml) , demonstrating the variant's functional impact on cytokine production across disease contexts.
Practical Implications
Your genotype at this position affects your baseline inflammatory tone and may influence susceptibility to autoimmune conditions. If you carry one or two G alleles, your immune system produces more IL-10, which generally suppresses inflammation but may contribute to certain autoimmune processes. This is neither universally good nor bad — context matters.
For those with autoimmune conditions, understanding your IL-10 production capacity can inform treatment approaches. The recent finding that G allele carriers respond better to biologic therapy in IBD suggests this variant may eventually help predict treatment outcomes.
The relationship between IL-10 levels and infection susceptibility is clinically relevant.
Patients with -1082 GG haplotype experienced more severe symptoms in community-acquired pneumonia and increased risk for septic shock compared to those with GA or AA genotypes , corresponding to higher IL-10 production dampening antimicrobial responses.
Interactions
The -1082 A>G variant functions as part of a three-SNP haplotype system with rs1800871 (-819 C>T) and rs1800872 (-592 C>A).
These form three principal haplotypes: GCC, ACC, and ATA, with GCC and ATA haplotypes associated with high and low IL-10 production respectively . The variants are in strong linkage disequilibrium and should be considered together for complete functional assessment.
When combined with TNF-α genotypes, IL-10 polymorphisms show stronger correlations with autoantibody production in SLE, particularly the combination of "low IL10 (-1082AA-AG)/high TNFα (-308AA-AG)" , suggesting gene-gene interactions between pro- and anti-inflammatory cytokine pathways influence disease manifestations.
Genotype Interpretations
What each possible genotype means for this variant:
Lower IL-10 production — baseline inflammatory regulation
You have two copies of the A allele at the IL10 -1082 position, associated with lower IL-10 production. About 35% of people of European descent share this genotype. Your immune system produces less of this anti-inflammatory cytokine, which means your inflammatory responses may be more robust but potentially less prone to the immune suppression seen with higher IL-10 levels. This is the ancestral configuration and represents normal immune function rather than a deficiency.
Moderate IL-10 production — balanced but potentially increased autoimmune risk
You have one copy of each allele, placing you in the intermediate IL-10 production category. About 48% of people of European descent have this genotype. Your IL-10 production falls between low and high producers, providing moderate anti-inflammatory capacity. This heterozygous state has been associated with increased risk for several autoimmune conditions including ankylosing spondylitis, rheumatoid arthritis, and inflammatory bowel disease, though the mechanisms vary by condition.
Elevated IL-10 production — strong anti-inflammatory response but increased autoimmune disease risk
The GG genotype creates a complex immunological situation. While high IL-10 effectively dampens acute inflammation and may protect against some inflammatory damage, it also promotes B-cell survival and drives antibody class switching. In autoimmune diseases, this can accelerate autoantibody production. Additionally, very high IL-10 levels during infections may overly suppress antimicrobial responses, potentially contributing to more severe illness from certain pathogens as demonstrated in pneumonia studies. Your immune system isn't deficient — it's operating with the volume turned up on one particular regulatory pathway, which has both advantages and disadvantages depending on the context.
Key References
AG and GG genotypes confer 3-fold increased risk for ankylosing spondylitis with elevated IL-10 levels
IL-10 -1082 G/A polymorphism determines inter-individual variation in IL-10 production
GG and AG genotypes associated with rheumatoid arthritis susceptibility in North Indian population
GG genotype associated with rheumatoid factor production in RA patients
IL10 rs1800896 variant allele predicts better response to biologic therapy in IBD patients