What you carry at this position in your DNA and what research says about it.
Inflammatory Disease Risk: 6/10 evidence, 55 publications.
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Sample genotype (not yours): G/G
Typical Risk of Inflammatory Conditions
Baseline levels of tumor necrosis factor expression are maintained by this common genetic profile. It is associated with a typical risk of developing chronic inflammatory conditions like psoriasis and Crohn's disease.
What this genotype means: Standard baseline risk of psoriasis; Typical susceptibility to Crohn's disease; Favorable response to anti-TNF therapies.
Sample genotype (not yours): A/A
Higher Risk of Inflammatory Conditions
Presence of two copies of the variant A allele is linked to significantly altered promoter activity and elevated cytokine expression. This rare profile is associated with the highest genetic susceptibility to chronic inflammatory diseases.
What this genotype means: Significantly increased risk of psoriasis; Higher susceptibility to Crohn's disease; Potentially reduced response to anti-TNF therapies.
Sample genotype (not yours): G/A
Elevated Risk of Inflammatory Conditions
Presence of one copy of the variant A allele is associated with altered promoter activity and increased cytokine expression. This profile is linked to a higher susceptibility to chronic inflammatory disorders such as psoriasis.
What this genotype means: Increased risk of psoriasis; Elevated susceptibility to Crohn's disease; Altered cytokine promoter activity.
Gene function and biological role
Gene Function: Tumor necrosis factor (TNF) encodes a multifunctional proinflammatory cytokine belonging to the tumor necrosis factor superfamily. This cytokine is mainly secreted by macrophages and plays a central role in regulating immune cells, inflammation, and programmed cell death [1]. Dysregulation of its production has been implicated in a variety of human diseases, including major autoimmune and inflammatory disorders [2]. It acts as a key mediator in systemic inflammation and is a primary target for several biological therapies used to treat chronic inflammatory conditions [3].
Variant Impact: Altering a single base at position -238 in the promoter region of the tumor necrosis factor gene, this change directly influences how the gene is transcribed. The substitution of guanine with adenine at this site affects transcription factor binding and modulates the level of cytokine expression [4]. Research indicates that the minor A allele is associated with altered local production of the cytokine and downstream inflammatory responses [5]. This functional change has been extensively studied for its role in modifying susceptibility to several chronic inflammatory and autoimmune diseases [2].
Key Insight: The variant allele at this position can increase the risk of psoriasis by over two-fold, particularly for early-onset cases.
Location: TNF. Chromosome 6 · 6p21.33 · 31.6 Mb
Estimated prevalence by population
Global 90.9%; European 89.9%; African 92.1%; East Asian 94.5%; South Asian 87.5%; Americas 90.2%; Ashkenazi 86.5%; Finnish 97.3%; Middle Eastern 88.1%; Amish 71.7%.
Estimated GG genotype frequency.
Global 8.9%; European 9.9%; African 7.8%; East Asian 5.4%; South Asian 12.1%; Americas 9.6%; Ashkenazi 13.0%; Finnish 2.7%; Middle Eastern 11.5%; Amish 26.0%.
Estimated GA genotype frequency.
Global 0.2%; European 0.3%; African 0.2%; East Asian 0.1%; South Asian 0.4%; Americas 0.3%; Ashkenazi 0.5%; Finnish < 0.1%; Middle Eastern 0.4%; Amish 2.4%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Organ Systems
Skin & Hair Conditions
Psoriasis. Evidence: 3/10. Source: PMID 24252077. Typical Risk.
Immunity & Inflammation
Chronic Inflammatory Diseases
Crohn's Disease. Evidence: 5/10. Source: PMID 37262302. Typical Risk.
Autoimmune Diseases
Ankylosing Spondylitis. Evidence: 3/10. Source: PMID 30208882. Typical Risk.
Pharmacogenomics
Immunosuppressant & Biologic Response
Anti-TNF Drug Response. Evidence: 6/10. Source: PMID 26244882. Stronger Response.
Showing effects for A/A genotype
Psoriasis. Evidence: 3/10. Source: PMID 24252077. Increased Risk.
Crohn's Disease. Evidence: 5/10. Source: PMID 37262302. Increased Risk.
Ankylosing Spondylitis. Evidence: 3/10. Source: PMID 30208882. Increased Risk.
Anti-TNF Drug Response. Evidence: 6/10. Source: PMID 26244882. Poorer Response.
Showing effects for G/A genotype
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Baseline levels of tumor necrosis factor expression are typically maintained by this common homozygous genotype. Individuals with this genetic profile do not experience the elevated risk of chronic inflammatory conditions associated with the variant allele [1]. Large-scale analyses show a standard baseline susceptibility to psoriasis and inflammatory bowel diseases [2]. Furthermore, clinical studies suggest that this genotype is associated with a more favorable response to anti-TNF therapies when treatment is required [3]. Maintaining a healthy lifestyle and managing systemic inflammation remains beneficial for overall wellness.
Standard baseline risk of psoriasis; Typical susceptibility to Crohn's disease; Favorable response to anti-TNF therapies.
Sample genotype: AA (Homozygous)
Significantly elevated promoter activity and increased cytokine production are characteristic of this rare homozygous genotype. Having two copies of the variant allele is strongly associated with an increased susceptibility to severe inflammatory disorders, including psoriasis and ankylosing spondylitis [1]. Research also demonstrates a higher risk of developing Crohn's disease compared to those with the common genotype [2]. Additionally, some clinical studies suggest that this genotype may be associated with a poorer response to certain anti-TNF biological treatments [3]. Proactive management of inflammatory triggers and close consultation with healthcare providers are important for individuals with this profile.
Significantly increased risk of psoriasis; Higher susceptibility to Crohn's disease; Potentially reduced response to anti-TNF therapies.
Sample genotype: GA (Heterozygous)
Altered promoter activity resulting from this heterozygous genotype can lead to increased expression of the tumor necrosis factor cytokine. This elevated inflammatory response is associated with a significantly higher risk of developing psoriasis, particularly early-onset forms of the condition [1]. Genetic studies also link this variant to an increased susceptibility to Crohn's disease and other chronic inflammatory bowel disorders [2]. Despite these elevated risks, clinical evidence indicates that individuals with this genotype generally retain a favorable response to anti-TNF biological therapies [3]. Monitoring for early symptoms of inflammatory conditions can help in timely management.
Increased risk of psoriasis; Elevated susceptibility to Crohn's disease; Altered cytokine promoter activity.
Variants with shared genetic architecture
rs1800629 · TNF Gene · Chr 6 · Inflammatory Response
rs1800610 · TNF Gene · Chr 6 · Type 2 Diabetes Risk
rs1800750 · TNF Gene · Chr 6 · Infection Susceptibility
Content updated August 2026.
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