What you carry at this position in your DNA and what research says about it.
Alzheimer's Disease Risk: 5/10 evidence, 54 publications.
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Sample genotype (not yours): C/C
Typical Risk of Alzheimer's Disease
Two copies of the common C allele are associated with typical baseline risks for neurodegenerative and inflammatory conditions. However, a poorer response to certain anti-inflammatory medications like adalimumab may occur.
What this genotype means: Typical baseline risk for Alzheimer's disease; Typical baseline risk for achalasia; Potentially poorer response to adalimumab therapy.
Sample genotype (not yours): C/T
Increased Risk of Alzheimer's Disease
One copy of the T allele is linked to an increased risk of Alzheimer's disease, which is further amplified in carriers of the APOE4 gene. It also correlates with a better clinical response to etanercept therapy.
What this genotype means: Increased risk of Alzheimer's disease; Synergistic risk increase when combined with APOE4; Potentially better response to etanercept therapy.
Sample genotype (not yours): T/T
Two copies of the T allele are linked to an increased risk of Alzheimer's disease, particularly when combined with the APOE4 gene. This profile also correlates with a more favorable response to etanercept.
Gene function and biological role
Gene Function: The LTA gene, encoding lymphotoxin alpha, is located in the major histocompatibility complex on chromosome six. It is closely linked to the tumor necrosis factor gene, which produces a key pro-inflammatory cytokine [1]. Lymphotoxin alpha plays a critical role in immune regulation, cell survival, and inflammatory pathways [2]. Genetic variations in this region can alter the expression levels of both lymphotoxin and tumor necrosis factor [1]. Consequently, these changes influence susceptibility to various autoimmune and inflammatory conditions [2].
Variant Impact: Located in the promoter region of the inflammatory locus, rs1799724 is a single nucleotide polymorphism [1]. This genetic change is also widely known as the TNF-857C/T polymorphism [3]. The presence of the T allele is associated with altered transcriptional activity and increased production of tumor necrosis factor alpha [1]. This heightened inflammatory response can influence how the body handles chronic inflammation and neurodegenerative processes [3].
Key Insight: The T allele acts as a genetic modifier that significantly amplifies Alzheimer's risk in people who also carry the APOE4 gene.
Location: LTA. Chromosome 6 · 6p21.33 · 31.6 Mb
Estimated prevalence by population
Global 83.4%; European 82.1%; African 93.9%; East Asian 75.3%; South Asian 77.0%; Americas 68.5%; Ashkenazi 55.4%; Finnish 89.2%; Middle Eastern 72.3%; Amish 84.2%.
Estimated CC genotype frequency.
Global 15.6%; European 17.0%; African 6.0%; East Asian 22.9%; South Asian 21.5%; Americas 28.5%; Ashkenazi 38.0%; Finnish 10.5%; Middle Eastern 25.5%; Amish 15.2%.
Estimated CT genotype frequency.
Global 1.0%; European 0.9%; African 0.1%; East Asian 1.7%; South Asian 1.5%; Americas 3.0%; Ashkenazi 6.5%; Finnish 0.3%; Middle Eastern 2.2%; Amish 0.7%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Neurology & Mental Health
Neurodegenerative Diseases
Alzheimer's Disease. Evidence: 4/10. Source: PMID 15895461. Typical Risk.
Pharmacogenomics
Immunosuppressant & Biologic Response
Etanercept Response. Evidence: 5/10. Source: PMID 15695296. Typical Response.
Adalimumab Response. Evidence: 5/10. Source: PMID 17673491. Poorer Response.
Organ Systems
Digestive & Gut Disorders
Achalasia. Evidence: 3/10. Source: PMID 24259423. Typical Risk.
Cancer & Oncology
Gastrointestinal Cancers
Gastric Cancer. Evidence: 4/10. Source: PMID 19615068. Typical Risk.
Showing effects for C/T genotype
Alzheimer's Disease. Evidence: 4/10. Source: PMID 15895461. Increased Risk.
Etanercept Response. Evidence: 5/10. Source: PMID 15695296. Stronger Response.
Adalimumab Response. Evidence: 5/10. Source: PMID 17673491. Typical Response.
Achalasia. Evidence: 3/10. Source: PMID 24259423. Increased Risk.
Gastric Cancer. Evidence: 4/10. Source: PMID 19615068. Increased Risk.
Showing effects for T/T genotype
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Representing the standard genetic baseline for the majority of the global population, two C alleles do not carry the elevated risk for late-onset Alzheimer's disease [1]. This protective baseline remains consistent regardless of whether an individual carries the high-risk APOE4 allele [1]. Additionally, this genotype is associated with a typical baseline risk for idiopathic achalasia, a rare swallowing disorder [2]. On the pharmacogenomic front, studies suggest that individuals with this genotype may experience a less optimal response to the TNF-inhibitor medication adalimumab [3]. Conversely, they exhibit a standard response profile to etanercept [4]. Maintaining a healthy lifestyle with regular exercise and a balanced diet supports overall brain and joint health. Discussing these findings with a healthcare provider can help clarify your overall health profile.
Typical baseline risk for Alzheimer's disease; Typical baseline risk for achalasia; Potentially poorer response to adalimumab therapy.
Sample genotype: CT (Heterozygous)
A moderate increase in the risk of developing late-onset Alzheimer's disease is associated with carrying one copy of the T allele [1]. Research indicates that the T allele interacts synergistically with the APOE4 allele, raising the risk of Alzheimer's significantly when both are present [1]. This genetic variant is also associated with altered levels of beta-amyloid in the cerebrospinal fluid, reflecting underlying neuroinflammatory changes [2]. Beyond cognitive health, carrying this allele is linked to a higher susceptibility to idiopathic achalasia, an inflammatory swallowing disorder [3].
Increased risk of Alzheimer's disease; Synergistic risk increase when combined with APOE4; Potentially better response to etanercept therapy.
Sample genotype: TT (Homozygous)
An elevated risk of developing late-onset Alzheimer's disease is linked to carrying two copies of the T allele due to increased neuroinflammation [1]. The presence of two T alleles is linked to higher production of tumor necrosis factor alpha, a key driver of inflammatory processes [2]. When combined with the APOE4 risk allele, the likelihood of developing Alzheimer's is substantially increased [1]. This genotype is also associated with lower levels of protective beta-amyloid in the cerebrospinal fluid [2]. Additionally, individuals carrying two copies of the T allele have an increased susceptibility to idiopathic achalasia [3]. On a positive note, this genetic profile is associated with a superior clinical response to etanercept therapy for inflammatory conditions [4]. Adopting an anti-inflammatory diet and maintaining physical activity can support long-term brain health. Discussing genetic profiles with a healthcare provider can help tailor personalized wellness strategies.
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
TNF polymorphisms in Alzheimer disease and functional implications on CSF beta-amyloid levels.
Content updated August 2026.
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