What you carry at this position in your DNA and what research says about it.
Autoimmune Disease Risk: 5/10 evidence, 25 publications.
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Sample genotype (not yours): G/G
Typical Risk of Autoimmune Conditions
Standard immune system regulation is typical for this genetic profile, which carries two copies of the common G allele. Baseline susceptibility to autoimmune conditions like celiac disease and rheumatoid arthritis remains at average population levels.
What this genotype means: Standard baseline risk for celiac disease; Standard baseline risk for rheumatoid arthritis; Better clinical response to rituximab therapy.
Sample genotype (not yours): G/T
Reduced Risk of Autoimmune Conditions
A single copy of the protective T allele naturally modulates immune responses, lowering the likelihood of developing several autoimmune disorders. Susceptibility to conditions like celiac disease and rheumatoid arthritis is reduced compared to the general population.
What this genotype means: Lower risk of developing celiac disease; Reduced susceptibility to rheumatoid arthritis; Decreased likelihood of inflammatory bowel disease.
Sample genotype (not yours): T/T
Significantly Lowered Risk of Autoimmune Conditions
An inheritance of two protective T alleles provides a strong genetic shield against multiple autoimmune disorders. The likelihood of developing conditions such as celiac disease, rheumatoid arthritis, and inflammatory bowel diseases is significantly reduced.
What this genotype means: Lowest genetic risk for celiac disease; Highly reduced susceptibility to rheumatoid arthritis; Strong protection against inflammatory bowel disease.
Gene function and biological role
Gene Function: The IL2 and IL21 genes encode key cytokines that regulate immune cell activation and survival. Interleukin-2 is critical for the development and maintenance of regulatory T-cells, which prevent the immune system from attacking the body's own tissues [1]. Interleukin-21 plays a major role in the differentiation of inflammatory T-cells and B-cell antibody production [2]. Together, these cytokines act as central orchestrators of immune tolerance and inflammatory responses. Dysregulation of this signaling pathway can lead to a breakdown in self-tolerance, promoting chronic inflammation and autoimmune reactions.
Variant Impact: The rs6822844 variant is an intergenic single nucleotide polymorphism located in the chromosomal region between the IL2 and IL21 genes. This genetic change does not alter the protein sequence directly but is thought to influence the expression levels of these neighboring cytokine genes [2]. By modulating how much interleukin-2 and interleukin-21 are produced, the variant alters the delicate balance of immune cell activation [3]. The major G allele is associated with typical cytokine expression and baseline susceptibility to several autoimmune conditions. Conversely, the minor T allele is associated with altered cytokine regulation that appears to protect against immune-mediated tissue damage.
Key Insight: The protective T allele is relatively rare globally, appearing in only about 10% of the population, but offers a broad shield against multiple distinct autoimmune conditions.
Location: IL2. Chromosome 4 · 4q27 · 122.6 Mb
Origin Story: Some evolutionary biologists suggest that the risk-associated G allele may have been maintained in populations because a highly active immune system helped ancestral humans fight off severe parasitic infections, despite the modern trade-off of increased autoimmune susceptibility.
Estimated prevalence by population
Global 81.1%; European 70.6%; African 94.4%; East Asian 99.8%; South Asian 84.8%; Americas 85.5%; Ashkenazi 82.9%; Finnish 79.9%; Middle Eastern 90.1%; Amish 66.9%.
Estimated GG genotype frequency.
Global 17.5%; European 26.9%; African 5.5%; East Asian 0.2%; South Asian 14.6%; Americas 13.9%; Ashkenazi 16.3%; Finnish 19.0%; Middle Eastern 9.7%; Amish 29.8%.
Estimated GT genotype frequency.
Global 1.4%; European 2.6%; African 0.1%; East Asian < 0.1%; South Asian 0.6%; Americas 0.6%; Ashkenazi 0.8%; Finnish 1.1%; Middle Eastern 0.3%; Amish 3.3%.
Estimated TT genotype frequency.
Showing effects for G/G genotype
Immunity & Inflammation
Autoimmune Diseases
Celiac Disease. Evidence: 5/10. Source: PMID 17558408. Typical Risk.
Rheumatoid Arthritis. Evidence: 4/10. Source: PMID 20553587. Typical Risk.
Chronic Inflammatory Diseases
Inflammatory Bowel Disease. Evidence: 4/10. Source: PMID 20445516. Typical Risk.
Cardiovascular & Metabolic
Diabetes & Glycemic Traits
Type 1 Diabetes. Evidence: 3/10. Source: PMID 21875375. Typical Risk.
Pharmacogenomics
Immunosuppressant & Biologic Response
Rituximab Response. Evidence: 5/10. Source: PMID 23645042. Stronger Response.
Showing effects for G/T genotype
Celiac Disease. Evidence: 5/10. Source: PMID 17558408. Lower Risk.
Rheumatoid Arthritis. Evidence: 4/10. Source: PMID 20553587. Lower Risk.
Inflammatory Bowel Disease. Evidence: 4/10. Source: PMID 20445516. Lower Risk.
Type 1 Diabetes. Evidence: 3/10. Source: PMID 21875375. Lower Risk.
Rituximab Response. Evidence: 5/10. Source: PMID 23645042. Typical Response.
Showing effects for T/T genotype
Celiac Disease. Evidence: 5/10. Source: PMID 17558408. Lowest Risk.
Rheumatoid Arthritis. Evidence: 4/10. Source: PMID 20553587. Lowest Risk.
Inflammatory Bowel Disease. Evidence: 4/10. Source: PMID 20445516. Lowest Risk.
Type 1 Diabetes. Evidence: 3/10. Source: PMID 21875375. Lowest Risk.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Immune system signaling operates at standard baseline levels with this common genetic profile. Large-scale genetic analyses show that the G allele represents the standard susceptibility baseline for several autoimmune disorders [1]. Research indicates that the typical G/G genotype is associated with standard rates of celiac disease, rheumatoid arthritis, and inflammatory bowel diseases compared to those carrying the protective T allele [2]. While it does not actively elevate risk above the general population average, it lacks the protective benefits against immune-mediated tissue damage seen with the minor T allele [3]. Interestingly, some clinical evidence suggests that this common profile may be linked to a more favorable response to certain immunotherapies, such as rituximab, in specific autoimmune contexts [4]. Overall, maintaining a balanced lifestyle and monitoring for common autoimmune symptoms is the standard approach for this typical genetic background.
Standard baseline risk for celiac disease; Standard baseline risk for rheumatoid arthritis; Better clinical response to rituximab therapy.
Sample genotype: GT (Heterozygous)
Natural protection against several autoimmune conditions is associated with carrying one copy of the minor T allele. Multiple genome-wide association studies have confirmed that this genetic variation significantly lowers the risk of developing celiac disease [1]. The protective effect extends to other inflammatory conditions, including rheumatoid arthritis and type 1 diabetes, by gently modulating cytokine signaling [2]. This genetic buffer helps prevent the immune system from overreacting and attacking the body's own tissues [3]. While the risk is reduced, it is not entirely eliminated, as environmental factors and other genetic loci still play a role in overall health. Some research also suggests a potential trade-off, where this protective profile might slightly alter responses to specific antibody-based immunotherapies [4]. Understanding this natural genetic shield highlights the complex ways the immune system maintains self-tolerance.
Lower risk of developing celiac disease; Reduced susceptibility to rheumatoid arthritis; Decreased likelihood of inflammatory bowel disease.
Sample genotype: TT (Homozygous)
Maximum genetic protection against autoimmune diseases is associated with carrying two copies of the protective T allele. This rare genetic profile is linked to the lowest susceptibility rates for celiac disease across multiple studied populations [1]. The double dose of the T allele also significantly reduces the risk of developing rheumatoid arthritis and inflammatory bowel diseases like Crohn's disease [2] [3]. By optimizing the regulation of interleukin cytokines, this profile helps maintain robust immune tolerance and prevents chronic inflammatory cascades [4]. Although autoimmune risk is minimized, maintaining a healthy lifestyle remains important since genetics is only one part of the puzzle. Some clinical studies indicate that this protective profile might also influence how the body responds to specific immunotherapies [5]. This unique genetic makeup represents an evolutionary adaptation that helps keep the immune system in a balanced, non-destructive state.
Lowest genetic risk for celiac disease; Highly reduced susceptibility to rheumatoid arthritis; Strong protection against inflammatory bowel disease.
Variants with shared genetic architecture
rs2069762 · IL2 Gene · Chr 4 · Autoimmune and Pain Response
rs2069763 · IL2 Gene · Chr 4 · Autoimmune and Asthma Risk
rs2069772 · IL2 Gene · Chr 4 · Allergy and Asthma Risk
Newly identified genetic risk variants for celiac disease related to the immune response.
Content updated August 2026.
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