What you carry at this position in your DNA and what research says about it.
Rheumatoid Arthritis Risk: 6/10 evidence, 53 publications.
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Sample genotype (not yours): T/T
Lower Rheumatoid Arthritis Risk
Two copies of the T allele are associated with lower baseline interleukin 18 levels, reducing the risk of rheumatoid arthritis. However, this genotype may elevate the risk of developing asthma.
What this genotype means: Lower risk of rheumatoid arthritis; Increased susceptibility to asthma; Better response to interferon therapy.
Sample genotype (not yours): G/G
Higher Rheumatoid Arthritis Risk
Two copies of the G allele lead to higher baseline interleukin 18 levels, increasing the risk of rheumatoid arthritis while offering protection against asthma.
What this genotype means: Increased risk of rheumatoid arthritis; Slower clearance of tacrolimus; Lower risk of pediatric asthma.
Sample genotype (not yours): T/G
Carrying one copy of the T allele provides protection against rheumatoid arthritis, though it slightly increases asthma susceptibility and slows tacrolimus clearance.
What this genotype means: Lower risk of rheumatoid arthritis; Slower metabolism of tacrolimus; Slightly increased asthma risk.
Gene function and biological role
Gene Function: The IL18 gene encodes interleukin 18, a powerful pro-inflammatory cytokine that belongs to the interleukin 1 superfamily. This protein is produced by various immune cells, including macrophages and dendritic cells, and plays a central role in regulating both innate and adaptive immunity. It acts as a key driver of inflammation by inducing the production of interferon-gamma and promoting helper T-cell differentiation. Because of its potent inflammatory properties, variations in this gene are widely studied for their roles in autoimmune disorders, chronic infections, and cancers.
Variant Impact: The rs1946518 variant is a single nucleotide change located in the promoter region of the IL18 gene, often referred to as the -607C/A polymorphism. This genetic change directly influences the binding of transcription factors, thereby modulating the rate of gene transcription and subsequent protein production [1]. The G allele corresponds to higher promoter activity and increased levels of circulating interleukin 18, whereas the T allele reduces promoter activity and leads to lower cytokine levels [1]. Consequently, this variant acts as a genetic dial for the body's baseline inflammatory response.
Key Insight: This single genetic variant acts as an evolutionary trade-off, where the allele that protects against joint inflammation simultaneously increases the risk of allergic airway diseases like asthma.
Location: IL18. Chromosome 11 · 11q23.1 · 112.2 Mb
Estimated prevalence by population
Global 16.7%; European 16.4%; African 13.0%; East Asian 27.2%; South Asian 10.0%; Americas 21.5%; Ashkenazi 26.2%; Finnish 21.4%; Middle Eastern 20.8%; Amish 14.7%.
Estimated TT genotype frequency.
Global 47.8%; European 48.2%; African 46.1%; East Asian 49.9%; South Asian 43.2%; Americas 49.7%; Ashkenazi 50.0%; Finnish 49.7%; Middle Eastern 49.6%; Amish 47.3%.
Estimated TG genotype frequency.
Global 35.4%; European 35.4%; African 40.9%; East Asian 22.9%; South Asian 46.8%; Americas 28.8%; Ashkenazi 23.8%; Finnish 28.8%; Middle Eastern 29.6%; Amish 38.0%.
Estimated GG genotype frequency.
Showing effects for T/T genotype
Immunity & Inflammation
Autoimmune Diseases
Rheumatoid Arthritis. Evidence: 4/10. Source: PMID 25192895. Lower Risk.
Organ Systems
Respiratory Health
Asthma. Evidence: 4/10. Source: PMID 31871417. Increased Risk.
Pharmacogenomics
Immunosuppressant & Biologic Response
Tacrolimus Clearance. Evidence: 6/10. Source: PMID 25487141. Typical Clearance.
Antimicrobial & Antiviral Response
Hepatitis C Treatment Response. Evidence: 5/10. Source: PMID 19455410. Stronger Response.
Showing effects for G/G genotype
Rheumatoid Arthritis. Evidence: 4/10. Source: PMID 25192895. Increased Risk.
Asthma. Evidence: 4/10. Source: PMID 31871417. Typical Risk.
Tacrolimus Clearance. Evidence: 6/10. Source: PMID 25487141. Slower Clearance.
Hepatitis C Treatment Response. Evidence: 5/10. Source: PMID 19455410. Poorer Response.
Showing effects for T/G genotype
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
This genotype is characterized by lower baseline production of the pro-inflammatory cytokine interleukin 18 [1]. Because of this reduced inflammatory drive, individuals with this genotype have a significantly lower risk of developing rheumatoid arthritis compared to those with the G/G genotype [2]. However, this lower cytokine level is also associated with an increased susceptibility to pediatric asthma and allergic airway inflammation [3]. In clinical settings, patients with this genotype who are treated for chronic hepatitis C have demonstrated a significantly better response to interferon-based therapies [1]. Additionally, this genotype is associated with typical clearance rates of the immunosuppressant drug tacrolimus.
Lower risk of rheumatoid arthritis; Increased susceptibility to asthma; Better response to interferon therapy.
Sample genotype: GG (Homozygous)
This genotype is associated with high promoter activity of the IL18 gene, leading to elevated baseline levels of interleukin 18 [1]. This heightened inflammatory state is linked to a significantly increased risk of developing rheumatoid arthritis and higher levels of inflammatory markers like C-reactive protein [2]. Interestingly, this robust immune response appears protective against allergic conditions, resulting in a lower risk of pediatric asthma [3]. In transplant medicine, this genotype is associated with slower clearance of tacrolimus, which can lead to higher drug exposure [4]. Furthermore, patients with this genotype have shown a poorer response rate to interferon-based therapies for hepatitis C [1].
Increased risk of rheumatoid arthritis; Slower clearance of tacrolimus; Lower risk of pediatric asthma.
Sample genotype: TG (Heterozygous)
This heterozygous genotype results in intermediate baseline levels of interleukin 18. Multiple meta-analyses indicate that carrying at least one T allele offers a protective effect against the development of rheumatoid arthritis [1]. Conversely, this same allele is associated with an increased risk of pediatric asthma and elevated total IgE levels [2]. From a pharmacological perspective, individuals with this genotype exhibit slower clearance of the immunosuppressant drug tacrolimus, which may raise its blood levels after transplantation [3]. On the other hand, this genotype is linked to a more favorable response to interferon and ribavirin therapy during hepatitis C treatment [4].
Lower risk of rheumatoid arthritis; Slower metabolism of tacrolimus; Slightly increased asthma risk.
Variants with shared genetic architecture
rs187238 · IL18 Gene · Chr 11 · Immune and Heart Health
rs1946519 · IL18 Gene · Chr 11 · Immune and Heart Health
rs1950897 · RAD51B Gene · Chr 14 · Rheumatoid Arthritis Risk
Association of IL-18 promoter gene polymorphisms with rheumatoid arthritis: a meta-analysis.
Content updated August 2026.
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