What you carry at this position in your DNA and what research says about it.
Heart Attack Risk: 5/10 evidence, 39 publications.
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Sample genotype (not yours): A/A
Lower Heart Attack Risk but Higher Asthma Sensitivity
Carrying two copies of the protective allele is associated with a lower risk of nonfatal heart attacks. However, this same genetic profile may increase the likelihood of developing asthma, particularly when using acetaminophen.
What this genotype means: Lower risk of nonfatal heart attacks; Increased sensitivity to acetaminophen-induced asthma; Higher levels of the TLR4:MD-2 immune complex.
Sample genotype (not yours): A/G
Carrying one copy of the protective allele is associated with a lower risk of nonfatal heart attacks. However, this genetic profile also carries an increased likelihood of asthma, especially in connection with acetaminophen use.
What this genotype means: Lower risk of nonfatal heart attacks; Increased sensitivity to acetaminophen-induced asthma; Moderately higher levels of the TLR4:MD-2 immune complex.
Sample genotype (not yours): G/G
Typical Heart Attack and Asthma Risk
Carrying two copies of the common G allele is associated with baseline risks for both heart attacks and asthma. There is no increased sensitivity to acetaminophen-induced respiratory issues.
What this genotype means: Typical baseline risk of heart attacks; Standard susceptibility to asthma; Typical levels of the TLR4:MD-2 immune complex.
Gene function and biological role
Gene Function: The TLR4 gene encodes Toll-like receptor 4, a critical protein in the innate immune system that detects bacterial pathogens and triggers inflammatory responses. It plays a key role in recognizing lipopolysaccharides from Gram-negative bacteria, initiating a signaling cascade that activates inflammatory cytokines. Beyond fighting infections, TLR4-mediated inflammation is heavily implicated in chronic conditions, including cardiovascular disease and asthma [1]. Variations in this gene can alter receptor expression or sensitivity, thereby modulating an individual's susceptibility to inflammatory disorders [2].
Variant Impact: The rs1927911 variant is an intronic change within the TLR4 gene that influences receptor expression and immune pathway activity. This genetic variation alters the levels of the TLR4:MD-2 complex, which is essential for ligand recognition and signal transduction [3]. By modulating the intensity of the body's inflammatory response, this variant affects the risk of inflammatory cardiovascular events and respiratory conditions [1]. It serves as a key genetic modifier of how the immune system reacts to environmental triggers and certain medications [2].
Key Insight: A genetic variant that helps protect the heart from inflammatory damage can simultaneously make the airways more sensitive to common over-the-counter pain relievers.
Location: TLR4. Chromosome 9 · 9q33.1 · 117.7 Mb
Estimated prevalence by population
Global 16.6%; European 6.5%; African 39.0%; East Asian 14.3%; South Asian 6.7%; Americas 10.5%; Ashkenazi 10.1%; Finnish 12.1%; Middle Eastern 8.0%; Amish 4.2%.
Estimated AA genotype frequency.
Global 42.0%; European 38.1%; African 46.9%; East Asian 47.0%; South Asian 38.3%; Americas 43.8%; Ashkenazi 43.4%; Finnish 45.4%; Middle Eastern 40.5%; Amish 32.5%.
Estimated AG genotype frequency.
Global 41.4%; European 55.4%; African 14.1%; East Asian 38.7%; South Asian 55.0%; Americas 45.6%; Ashkenazi 46.6%; Finnish 42.5%; Middle Eastern 51.5%; Amish 63.3%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Cardiovascular & Metabolic
Heart Disease
Heart Attack. Evidence: 3/10. Source: PMID 25590839. ~12% Lower Risk.
Stroke
Stroke. Evidence: 3/10. Source: PMID 25590839. Altered Risk.
Organ Systems
Respiratory Health
Asthma. Evidence: 5/10. Source: PMID 24851022. Increased Risk.
Immunity & Inflammation
Inflammatory & Circulating Protein Markers
Immune Complex Levels. Evidence: 4/10. Source: PMID 36168886. Higher Levels.
Showing effects for A/G genotype
Immune Complex Levels. Evidence: 4/10. Source: PMID 36168886. Intermediate Levels.
Showing effects for G/G genotype
Heart Attack. Evidence: 3/10. Source: PMID 25590839. Typical Risk.
Stroke. Evidence: 3/10. Source: PMID 25590839. Typical Risk.
Asthma. Evidence: 5/10. Source: PMID 24851022. Typical Risk.
Immune Complex Levels. Evidence: 4/10. Source: PMID 36168886. Typical Levels.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
This genotype is linked to a reduced risk of experiencing a nonfatal heart attack, likely due to altered inflammatory signaling in the cardiovascular system [1]. Research indicates that the minor A allele helps temper the chronic blood vessel inflammation that contributes to arterial plaque buildup and subsequent cardiac events [1]. However, this altered immune response has a trade-off in the respiratory system. Individuals with this genotype show an increased susceptibility to childhood asthma and bronchial hyperresponsiveness, especially when exposed to environmental triggers like traffic-related air pollution [2]. Furthermore, there is a documented interaction with acetaminophen, where use of this common pain reliever is associated with a higher likelihood of asthma development [3]. This suggests that while the genotype protects the heart, it may make the airways more sensitive to inflammatory stimuli.
Lower risk of nonfatal heart attacks; Increased sensitivity to acetaminophen-induced asthma; Higher levels of the TLR4:MD-2 immune complex.
Sample genotype: AG (Heterozygous)
Having one copy of the A allele provides a similar protective effect against nonfatal heart attacks as having two copies [1]. This protective mechanism is thought to stem from a moderation of vascular inflammation, which helps maintain healthier blood vessels over time [1]. On the other hand, the single A allele also influences respiratory health by predisposing individuals to airway inflammation. Studies have shown that carriers of this allele are more vulnerable to the adverse respiratory effects of traffic-related air pollution [2]. Additionally, clinical research has identified a significant interaction with acetaminophen, showing that recent use of the medication is linked to an elevated risk of asthma in individuals with this genotype [3]. Consequently, managing environmental exposures and monitoring respiratory health is particularly relevant for carriers.
Lower risk of nonfatal heart attacks; Increased sensitivity to acetaminophen-induced asthma; Moderately higher levels of the TLR4:MD-2 immune complex.
Sample genotype: GG (Homozygous)
This genotype represents the common baseline genetic profile for this variant, showing typical risks for cardiovascular and respiratory conditions. Unlike carriers of the minor A allele, individuals with this genotype do not experience the slight reduction in nonfatal heart attack risk [1]. However, they also do not carry the elevated risk of developing asthma associated with environmental pollutants or acetaminophen use [2] [3]. The immune system's TLR4 receptors function at typical baseline levels, maintaining standard inflammatory responses to pathogens and environmental triggers. There are no specific dietary or medication modifications recommended based on this genotype, as it reflects the standard population average.
Typical baseline risk of heart attacks; Standard susceptibility to asthma; Typical levels of the TLR4:MD-2 immune complex.
Variants with shared genetic architecture
rs1928295 · TLR4 Gene · Chr 9 · Weight and Obesity Risk
rs4986790 · TLR4 Gene · Chr 9 · Infection and Heart Risk
rs4986791 · TLR4 Gene · Chr 9 · Infection and Immune Response
Association between recent acetaminophen use and asthma: modification by polymorphism at TLR4.
Content updated August 2026.
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