What you carry at this position in your DNA and what research says about it.
Inflammation and Allergies: 9/10 evidence, 28 publications.
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Sample genotype (not yours): A/A
Higher Rheumatoid Arthritis Risk
Higher levels of systemic inflammation markers are common with this profile. This leads to an elevated risk of rheumatoid arthritis but offers some protection against allergic conditions.
What this genotype means: Elevated risk of rheumatoid arthritis; Higher baseline C-reactive protein levels; Lower risk of asthma and eczema.
Sample genotype (not yours): A/C
Typical Inflammation and Allergy Risk
A balanced genetic profile results in typical levels of systemic inflammation and allergic sensitivity. Most health risks associated with this gene remain at average baseline levels.
What this genotype means: Average risk of rheumatoid arthritis; Typical baseline inflammation levels; Average susceptibility to allergies.
Sample genotype (not yours): C/C
Lower Rheumatoid Arthritis Risk but Higher Allergy Risk
Dampened systemic inflammation provides strong protection against rheumatoid arthritis. However, this same mechanism increases susceptibility to asthma, eczema, and hay fever.
What this genotype means: Reduced risk of rheumatoid arthritis; Lower baseline C-reactive protein levels; Increased risk of asthma, eczema, and hay fever.
Gene function and biological role
Gene Function: Interleukin 6 receptor (IL6R) is a critical component of the immune system that binds to the pro-inflammatory cytokine interleukin-6 [1]. This binding initiates a signaling cascade that regulates systemic inflammation, immune cell activation, and the acute-phase response [1] [2]. The receptor exists in two forms: a membrane-bound version that drives classic inflammatory signaling, and a soluble version that can circulate in the blood [2]. Dysregulation of this pathway is heavily implicated in chronic inflammatory diseases, autoimmune disorders, and cardiovascular conditions [2] [3]. Therapeutic targeting of this receptor is a common strategy to treat severe inflammatory conditions like rheumatoid arthritis [3].
Variant Impact: This missense variant, known as p.Asp358Ala, alters the amino acid sequence of the interleukin-6 receptor, changing an aspartate to an alanine [2]. This structural alteration occurs at a key cleavage site, significantly increasing the rate at which the receptor is shed from cell membranes [2] [4]. As a result, membrane-bound receptors are depleted, which impairs classic inflammatory signaling in immune cells [4]. Conversely, the shedding process dramatically increases the concentration of soluble receptor subunits circulating in the blood [2] [4]. This functional shift creates a unique genetic profile that simultaneously dampens systemic inflammation while altering susceptibility to allergic responses [4] [5].
Key Insight: This variant acts like a natural version of the arthritis drug tocilizumab, lowering systemic inflammation but raising allergy risks.
Location: IL6R. Chromosome 1 · 1q21.3 · 154.5 Mb
Estimated prevalence by population
Global 47.6%; European 36.7%; African 74.8%; East Asian 40.8%; South Asian 50.4%; Americas 26.1%; Ashkenazi 34.6%; Finnish 51.9%; Middle Eastern 38.3%; Amish 27.9%.
Estimated AA genotype frequency.
Global 40.5%; European 47.7%; African 23.4%; East Asian 46.2%; South Asian 41.2%; Americas 50.0%; Ashkenazi 48.4%; Finnish 40.3%; Middle Eastern 47.2%; Amish 49.8%.
Estimated AC genotype frequency.
Global 11.8%; European 15.5%; African 1.8%; East Asian 13.1%; South Asian 8.4%; Americas 23.9%; Ashkenazi 16.9%; Finnish 7.8%; Middle Eastern 14.5%; Amish 22.2%.
Estimated CC genotype frequency.
Showing effects for A/A genotype
Immunity & Inflammation
Autoimmune Diseases
Rheumatoid Arthritis. Evidence: 6/10. Source: PMID 24390342. ~1.16x Higher Risk.
Inflammatory & Circulating Protein Markers
C-Reactive Protein. Evidence: 9/10. Source: PMID 31217584. Higher Levels.
Allergy & Hypersensitivity
Allergic Rhinitis. Evidence: 8/10. Source: PMID 31361310. Reduced Risk.
Organ Systems
Respiratory Health
Asthma. Evidence: 8/10. Source: PMID 31361310. Reduced Risk.
Skin & Hair Conditions
Eczema. Evidence: 9/10. Source: PMID 30595370. Reduced Risk.
Pharmacogenomics
Pain Medication Response
Morphine Side Effects. Evidence: 5/10. Source: PMID 38824169. Typical Likelihood.
Showing effects for A/C genotype
Rheumatoid Arthritis. Evidence: 6/10. Source: PMID 24390342. Typical Risk.
C-Reactive Protein. Evidence: 9/10. Source: PMID 31217584. Typical Levels.
Allergic Rhinitis. Evidence: 8/10. Source: PMID 31361310. Typical Risk.
Asthma. Evidence: 8/10. Source: PMID 31361310. Typical Risk.
Eczema. Evidence: 9/10. Source: PMID 30595370. Typical Risk.
Morphine Side Effects. Evidence: 5/10. Source: PMID 38824169. Lower Likelihood.
Showing effects for C/C genotype
Rheumatoid Arthritis. Evidence: 6/10. Source: PMID 24390342. Reduced Risk.
C-Reactive Protein. Evidence: 9/10. Source: PMID 31217584. Lower Levels.
Allergic Rhinitis. Evidence: 8/10. Source: PMID 31361310. ~1.08x Higher Risk.
Asthma. Evidence: 8/10. Source: PMID 31361310. ~1.1x Higher Risk.
Eczema. Evidence: 9/10. Source: PMID 30595370. ~1.16x Higher Risk.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Classic inflammatory signaling remains fully active because the interleukin-6 receptor is stably anchored to immune cell membranes [1]. This stable anchoring results in higher baseline levels of systemic inflammation markers like C-reactive protein [2]. Consequently, there is a moderately increased risk of developing rheumatoid arthritis and other chronic inflammatory conditions [3]. However, because classic inflammatory pathways are fully functional, the immune system is less prone to the specific dysregulations that trigger allergic reactions [4]. This translates to a lower likelihood of developing asthma, eczema, and hay fever [4]. Additionally, when taking morphine for pain management, there is a typical likelihood of experiencing side effects like nausea and fatigue [5].
Elevated risk of rheumatoid arthritis; Higher baseline C-reactive protein levels; Lower risk of asthma and eczema.
Sample genotype: AC (Heterozygous)
Carrying one copy of each allele produces a balanced mix of membrane-bound and soluble interleukin-6 receptors [1]. Systemic inflammatory signaling operates at a typical baseline level, resulting in average concentrations of C-reactive protein [2]. The risk for rheumatoid arthritis is not significantly elevated, remaining close to the general population average [3]. Similarly, susceptibility to allergic conditions like asthma, eczema, and hay fever is typical [4]. This intermediate state avoids the higher inflammatory risks of one extreme and the allergic sensitivities of the other [3] [4]. Furthermore, individuals with this profile may experience a decreased likelihood of side effects like nausea and fatigue when using morphine [5].
Average risk of rheumatoid arthritis; Typical baseline inflammation levels; Average susceptibility to allergies.
Sample genotype: CC (Homozygous)
Accelerated shedding of the interleukin-6 receptor from cell membranes significantly reduces classic inflammatory signaling [1]. This reduction in membrane-bound receptors leads to lower baseline levels of systemic inflammation markers, including C-reactive protein [2]. As a result, there is a robust protective effect against developing rheumatoid arthritis and coronary heart disease [3]. However, the dramatic increase in circulating soluble receptors alters immune responses in a way that promotes allergic sensitivity [4]. This significantly raises the risk of developing asthma, eczema, and allergic rhinitis [4]. On the therapeutic side, this profile is associated with a decreased likelihood of experiencing nausea, fatigue, or depression when treated with morphine [5].
Reduced risk of rheumatoid arthritis; Lower baseline C-reactive protein levels; Increased risk of asthma, eczema, and hay fever.
Variants with shared genetic architecture
rs4129267 · IL6R Gene · Chr 1 · Asthma and Inflammation Risk
rs12083537 · IL6R Gene · Chr 1 · Systemic Inflammation
rs4537545 · IL6R Gene · Chr 1 · Heart Disease Risk
Genetics of rheumatoid arthritis contributes to biology and drug discovery.
Admixture mapping of an allele affecting interleukin 6 soluble receptor and interleukin 6 levels.
Genetic analyses of diverse populations improves discovery for complex traits.
Content updated August 2026.
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