What you carry at this position in your DNA and what research says about it.
Inflammatory Disease Risk: 4/10 evidence, 54 publications.
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Sample genotype (not yours): A/A
Typical Inflammatory Risk Profile
Two copies of the A allele are associated with baseline levels of lymphotoxin-alpha. This translates to a typical or lower risk for several chronic inflammatory conditions.
What this genotype means: Typical risk of psoriatic arthritis; Lower susceptibility to asthma.
Sample genotype (not yours): A/G
Moderately Elevated Inflammatory Risk
Carrying one copy of the G allele is linked to moderately increased levels of lymphotoxin-alpha. This can elevate the risk for inflammatory and autoimmune conditions.
What this genotype means: Moderately increased risk of asthma; Slightly higher susceptibility to periodontitis.
Sample genotype (not yours): G/G
Highest Inflammatory Risk Profile
Two copies of the G allele are associated with the highest levels of lymphotoxin-alpha. This significantly increases susceptibility to chronic inflammatory diseases.
What this genotype means: Highest risk of psoriatic arthritis; Increased susceptibility to chronic periodontitis.
Gene function and biological role
Gene Function: The LTA gene provides instructions for producing lymphotoxin-alpha, a pro-inflammatory signaling protein belonging to the tumor necrosis factor family [1]. This cytokine plays a vital role in organizing lymphoid tissues and regulating immune responses [1]. It helps coordinate the body's defense mechanisms against infections and cellular damage [2]. However, when lymphotoxin-alpha is produced in excess, it can drive chronic, tissue-damaging inflammation [2]. Consequently, variations in this gene are frequently studied for their roles in autoimmune and inflammatory conditions [3].
Variant Impact: The rs909253 variant, often referred to as the +252A/G or NcoI polymorphism, is located in the first intron of the LTA gene [1]. This specific genetic change is functional and has been shown to influence the transcriptional activity of the gene [4]. Carrying the G allele is associated with increased expression and higher circulating levels of lymphotoxin-alpha [4]. This elevated cytokine production can amplify inflammatory pathways, making carriers more susceptible to various immune-mediated diseases [2].
Key Insight: The G allele acts as a double-edged sword, increasing the risk for several inflammatory conditions like psoriatic arthritis and asthma, while simultaneously offering protection against ankylosing spondylitis.
Location: LTA. Chromosome 6 · 6p21.33 · 31.6 Mb
Estimated prevalence by population
Global 38.4%; European 43.6%; African 24.1%; East Asian 27.3%; South Asian 51.9%; Americas 42.2%; Ashkenazi 57.6%; Finnish 47.7%; Middle Eastern 46.0%; Amish 39.9%.
Estimated AA genotype frequency.
Global 46.0%; European 44.8%; African 50.0%; East Asian 49.9%; South Asian 40.3%; Americas 45.5%; Ashkenazi 36.6%; Finnish 42.7%; Middle Eastern 43.7%; Amish 46.5%.
Estimated AG genotype frequency.
Global 15.6%; European 11.5%; African 25.9%; East Asian 22.8%; South Asian 7.8%; Americas 12.3%; Ashkenazi 5.8%; Finnish 9.5%; Middle Eastern 10.4%; Amish 13.5%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Immunity & Inflammation
Autoimmune Diseases
Psoriatic Arthritis. Evidence: 3/10. Source: PMID 12746914. Typical Risk.
Organ Systems
Respiratory Health
Asthma. Evidence: 4/10. Source: PMID 22882567. Typical Risk.
Dental & Oral Health
Periodontitis. Evidence: 3/10. Source: PMID 23050158. Typical Risk.
Cancer & Oncology
Gastrointestinal Cancers
Gastric Cancer. Evidence: 4/10. Source: PMID 22748850. Typical Risk.
Showing effects for A/G genotype
Psoriatic Arthritis. Evidence: 3/10. Source: PMID 12746914. Increased Risk.
Asthma. Evidence: 4/10. Source: PMID 22882567. Increased Risk.
Periodontitis. Evidence: 3/10. Source: PMID 23050158. Increased Risk.
Gastric Cancer. Evidence: 4/10. Source: PMID 22748850. Increased Risk.
Showing effects for G/G genotype
Psoriatic Arthritis. Evidence: 3/10. Source: PMID 12746914. Highest Risk.
Asthma. Evidence: 4/10. Source: PMID 22882567. Highest Risk.
Periodontitis. Evidence: 3/10. Source: PMID 23050158. Highest Risk.
Gastric Cancer. Evidence: 4/10. Source: PMID 22748850. Highest Risk.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Carrying the A/A genotype means having the baseline genetic profile for lymphotoxin-alpha expression. Because this genotype does not cause the elevated cytokine levels associated with the G allele, it is generally protective against several inflammatory conditions [1]. Studies indicate a lower susceptibility to psoriatic arthritis and asthma compared to carriers of the G allele [2]. Additionally, this genotype is associated with a typical risk for periodontal disease and certain cancers [3]. However, some research suggests a slightly higher baseline susceptibility to ankylosing spondylitis compared to those with the G/G genotype.
Typical risk of psoriatic arthritis; Lower susceptibility to asthma.
Sample genotype: AG (Heterozygous)
Having the A/G genotype means carrying one copy of the pro-inflammatory G allele. This single copy is sufficient to moderately increase the expression of lymphotoxin-alpha, leading to a more active immune response [1]. Clinical studies have linked this genotype to an increased risk of developing psoriatic arthritis and asthma [2]. There is also a documented rise in susceptibility to chronic periodontitis, as the heightened inflammatory state can affect gum health [3]. While the risk is elevated, lifestyle factors and overall health play a major role in whether these conditions manifest.
Moderately increased risk of asthma; Slightly higher susceptibility to periodontitis.
Sample genotype: GG (Homozygous)
Carrying the G/G genotype leads to the highest transcriptional activity of the LTA gene, resulting in elevated levels of the pro-inflammatory cytokine lymphotoxin-alpha [1]. This persistent inflammatory environment significantly increases the risk of developing psoriatic arthritis and asthma [2]. Research also shows a strong association with chronic periodontitis, where the body's overactive immune response can accelerate tissue damage in the gums [3]. Interestingly, while this genotype predisposes to many inflammatory issues, some studies suggest it may offer a protective effect against ankylosing spondylitis.
Highest risk of psoriatic arthritis; Increased susceptibility to chronic periodontitis.
Variants with shared genetic architecture
rs2229094 · LTA Gene · Chr 6 · Gastric Cancer Risk
rs1799964 · LTA Gene · Chr 6 · Inflammatory Disease Risk
rs1800630 · LTA Gene · Chr 6 · Autoimmune Disease Risk
The +252A/G polymorphism in the lymphotoxin-α gene increases the risk of asthma: a meta-analysis.
Cytokine gene polymorphisms: association with psoriatic arthritis susceptibility and severity.
Content updated August 2026.
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