What you carry at this position in your DNA and what research says about it.
Blood Pressure: 9/10 evidence, 21 publications.
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Sample genotype (not yours): G/G
Typical Blood Pressure and Lower Hypertension Risk
Favorable systolic and diastolic blood pressure measurements are associated with this genetic profile. It represents the baseline that avoids the blood pressure-raising effects of the A allele.
What this genotype means: Lower systolic and diastolic blood pressure; Slightly higher risk of psoriasis; Increased risk of skin rash if taking gefitinib.
Sample genotype (not yours): A/A
Increased Blood Pressure Risk
Higher systolic and diastolic blood pressure measurements are linked to this two-copy profile. However, it provides a lower risk of developing psoriasis.
What this genotype means: Higher systolic and diastolic blood pressure; Lower risk of psoriasis; Typical risk of skin rash if taking gefitinib.
Sample genotype (not yours): G/A
Slightly Increased Blood Pressure Risk
A minor increase in systolic and diastolic blood pressure is associated with this single-copy profile. It also slightly reduces the risk of developing psoriasis.
What this genotype means: Slightly higher systolic and diastolic blood pressure; Slightly lower risk of psoriasis; Increased risk of skin rash if taking gefitinib.
Gene function and biological role
Gene Function: The NFKBIA gene encodes the IkappaBalpha protein, which serves as a major cellular brake on inflammatory processes [1]. It works by binding to and sequestering the NF-kappaB transcription factor complex in the cytoplasm, keeping it inactive [1]. When cells receive inflammatory signals, IkappaBalpha is targeted for rapid degradation, allowing NF-kappaB to enter the nucleus and activate genes involved in immune responses and cell survival [1]. Because of this central role, variations in NFKBIA can alter the baseline level of inflammation in the body [2]. This altered inflammatory state is linked to various cardiovascular and autoimmune conditions [2].
Variant Impact: The rs8904 variant is located in the 3 prime untranslated region of the NFKBIA gene, a region critical for regulating gene expression and mRNA stability. This genetic change is thought to influence how efficiently the IkappaBalpha protein is produced, thereby subtly shifting the body's inflammatory baseline. Because inflammation plays a key role in vascular health, this variant has been heavily studied in large-scale genetic analyses of cardiovascular traits. It is most notably associated with variations in blood pressure, including systolic and diastolic measurements. Additionally, it shows minor links to autoimmune skin conditions and drug sensitivities.
Key Insight: While the A allele slightly increases blood pressure, it simultaneously lowers the risk of developing the autoimmune skin condition psoriasis.
Location: NFKBIA. Chromosome 14 · 14q13.2 · 35.4 Mb
Estimated prevalence by population
Global 32.6%; European 38.6%; African 16.4%; East Asian 36.3%; South Asian 32.2%; Americas 44.1%; Ashkenazi 36.2%; Finnish 35.8%; Middle Eastern 28.9%; Amish 62.3%.
Estimated GG genotype frequency.
Global 47.2%; European 47.1%; African 48.2%; East Asian 47.9%; South Asian 49.1%; Americas 44.6%; Ashkenazi 47.9%; Finnish 48.1%; Middle Eastern 49.7%; Amish 33.2%.
Estimated GA genotype frequency.
Global 20.1%; European 14.3%; African 35.4%; East Asian 15.8%; South Asian 18.7%; Americas 11.3%; Ashkenazi 15.9%; Finnish 16.1%; Middle Eastern 21.4%; Amish 4.4%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Cardiovascular & Metabolic
Hypertension
Systolic Blood Pressure. Evidence: 9/10. Source: PMID 38689001. Typical.
Pulse Pressure. Evidence: 9/10. Source: PMID 38689001. Typical.
Diastolic Blood Pressure. Evidence: 8/10. Source: PMID 38689001. Typical.
Heart Rhythm & Conduction
Cardiac Conduction. Evidence: 6/10. Source: PMID 32439900. +0.4 ms PR Interval.
Organ Systems
Skin & Hair Conditions
Psoriasis. Evidence: 7/10. Source: PMID 39885523. Increased Risk.
Pharmacogenomics
Chemotherapy Response
Gefitinib Skin Rash. Evidence: 5/10. Source: PMID 31664190. Increased Risk.
Lifestyle, Fitness & Aging
Muscle Strength & Power
Appendicular Lean Mass. Evidence: 6/10. Source: PMID 33097823. Increased Mass.
Showing effects for A/A genotype
Systolic Blood Pressure. Evidence: 9/10. Source: PMID 38689001. +0.42 mmHg.
Pulse Pressure. Evidence: 9/10. Source: PMID 38689001. +0.34 mmHg.
Diastolic Blood Pressure. Evidence: 8/10. Source: PMID 38689001. Higher.
Cardiac Conduction. Evidence: 6/10. Source: PMID 32439900. -0.4 ms PR Interval.
Psoriasis. Evidence: 7/10. Source: PMID 39885523. Decreased Risk.
Gefitinib Skin Rash. Evidence: 5/10. Source: PMID 31664190. Typical Risk.
Appendicular Lean Mass. Evidence: 6/10. Source: PMID 33097823. Decreased Mass.
Showing effects for G/A genotype
Systolic Blood Pressure. Evidence: 9/10. Source: PMID 38689001. +0.21 mmHg.
Pulse Pressure. Evidence: 9/10. Source: PMID 38689001. +0.17 mmHg.
Diastolic Blood Pressure. Evidence: 8/10. Source: PMID 38689001. Slightly Higher.
Cardiac Conduction. Evidence: 6/10. Source: PMID 32439900. Typical.
Psoriasis. Evidence: 7/10. Source: PMID 39885523. Typical.
Appendicular Lean Mass. Evidence: 6/10. Source: PMID 33097823. Typical.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Double copies of the G allele are linked to more favorable blood pressure levels compared to the A allele [1]. Large-scale genome-wide association studies involving hundreds of thousands of individuals have demonstrated that the G allele is associated with lower systolic, diastolic, and pulse pressure measurements [1] [2]. This protective effect is thought to stem from more stable regulation of the NF-kappaB inflammatory pathway, which helps maintain healthy blood vessel function [3]. However, this genotype is also associated with a slightly higher risk of developing psoriasis [4]. Additionally, in lung cancer patients treated with the medication gefitinib, carrying the G/G genotype has been linked to an increased risk of developing a skin rash [5]. Despite these minor trade-offs, the overall cardiovascular profile remains highly favorable [1].
Lower systolic and diastolic blood pressure; Slightly higher risk of psoriasis; Increased risk of skin rash if taking gefitinib.
Sample genotype: AA (Homozygous)
Two copies of the A allele are consistently linked to elevated blood pressure measurements in extensive genetic studies [1]. In these large cohorts, this genotype is associated with the highest systolic, diastolic, and pulse pressure measurements [1] [2]. The increased pressure may result from altered expression of the IkappaBalpha inhibitor, leading to slightly higher vascular inflammation [3]. Conversely, the A/A genotype is associated with a significantly lower risk of psoriasis compared to G/G carriers [4]. It also represents the typical, non-elevated risk profile for skin rashes when undergoing gefitinib therapy [5]. While the blood pressure increase per allele is small, managing lifestyle factors remains important for overall cardiovascular health [1].
Higher systolic and diastolic blood pressure; Lower risk of psoriasis; Typical risk of skin rash if taking gefitinib.
Sample genotype: GA (Heterozygous)
A single copy of the blood pressure-raising A allele is present in this genotype [1]. Research across multiple large cohorts indicates that each copy of the A allele incrementally increases systolic and pulse pressure [1] [2]. This effect is believed to be mediated by subtle changes in vascular inflammation regulated by the NFKBIA gene [3]. On the positive side, carrying one A allele is associated with a lower risk of the autoimmune skin condition psoriasis compared to the G/G genotype [4]. For individuals prescribed the cancer drug gefitinib, this genotype is also associated with an elevated risk of experiencing a skin rash [5]. Overall, the cardiovascular impact is modest but represents a slight elevation over the baseline [1].
Slightly higher systolic and diastolic blood pressure; Slightly lower risk of psoriasis; Increased risk of skin rash if taking gefitinib.
Variants with shared genetic architecture
rs8016947 · NFKBIA Gene · Chr 14 · Psoriasis Risk
rs696 · NFKBIA Gene · Chr 14 · Inflammatory Response and Health
rs2233406 · NFKBIA Gene · Chr 14 · Infection Susceptibility
Polymorphisms in NF-kappaB inhibitors and risk of epithelial ovarian cancer.
Toll-like receptor 1 polymorphisms affect innate immune responses and outcomes in sepsis.
Trans-ethnic association study of blood pressure determinants in over 750,000 individuals.
Content updated August 2026.
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