What you carry at this position in your DNA and what research says about it.
Heart Disease Risk: 10/10 evidence, 54 publications.
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Sample genotype (not yours): A/A
Higher Risk of Heart Disease
Higher levels of circulating adhesion molecules are characteristic of this profile. This elevation is linked to an increased susceptibility to coronary artery disease and heart attacks.
What this genotype means: Higher levels of circulating soluble ICAM-1; Increased susceptibility to coronary artery disease.
Sample genotype (not yours): A/G
Lower Risk of Heart Disease
Reduced levels of circulating adhesion molecules help protect blood vessels under this profile. This change is linked to a decreased risk of coronary artery disease.
What this genotype means: Lower levels of circulating soluble ICAM-1; Decreased risk of coronary artery disease; Reduced risk of diabetic nephropathy in females.
Sample genotype (not yours): G/G
Lower Heart Risk but Higher Malaria Risk
Significant protection against coronary artery disease and diabetic kidney complications is a key feature of this profile. However, it may also increase susceptibility to severe malaria infections in endemic areas.
What this genotype means: Lowest levels of circulating soluble ICAM-1; Significantly decreased risk of coronary artery disease; Increased susceptibility to severe malaria in endemic regions.
Gene function and biological role
Gene Function: The ICAM1 gene encodes intercellular adhesion molecule 1, a cell surface glycoprotein typically expressed on endothelial and immune cells [1]. This protein plays a critical role in directing white blood cells to sites of inflammation and injury [2]. By facilitating the adhesion and migration of immune cells through blood vessel walls, it helps coordinate the body's inflammatory response [3]. However, excessive or prolonged expression of this molecule can contribute to chronic inflammatory conditions and cardiovascular issues [4]. It also serves as an entry receptor for certain pathogens, including the malaria parasite [5].
Variant Impact: The rs5498 variant is a missense mutation in exon 6 of the ICAM1 gene, resulting in an amino acid substitution from lysine to glutamate at position 469 [1]. This structural alteration occurs in the immunoglobulin-like domain 5 of the protein, which is involved in receptor dimerization and cell-to-cell interactions [2]. The change directly influences how the protein folds and interacts with its binding partners on other cells [3]. Consequently, this variant alters the levels of soluble ICAM-1 circulating in the bloodstream and modifies the adhesion properties of vascular walls [6].
Key Insight: A single genetic change in the ICAM1 gene can simultaneously lower the risk of heart attacks while increasing susceptibility to severe malaria, demonstrating a classic evolutionary trade-off.
Location: ICAM1. Chromosome 19 · 19p13.2 · 10.3 Mb
Origin Story: The G allele of rs5498 is thought to have been maintained in certain human populations due to balancing selection, where the cardiovascular benefits of lower inflammation trade off against altered susceptibility to infectious pathogens like malaria.
Estimated prevalence by population
Global 41.0%; European 32.1%; African 66.4%; East Asian 50.9%; South Asian 27.2%; Americas 25.0%; Ashkenazi 27.8%; Finnish 29.1%; Middle Eastern 38.3%; Amish 18.8%.
Estimated AA genotype frequency.
Global 43.8%; European 49.1%; African 30.2%; East Asian 40.9%; South Asian 49.9%; Americas 50.0%; Ashkenazi 49.8%; Finnish 49.7%; Middle Eastern 47.2%; Amish 49.1%.
Estimated AG genotype frequency.
Global 15.3%; European 18.7%; African 3.4%; East Asian 8.2%; South Asian 22.9%; Americas 25.0%; Ashkenazi 22.3%; Finnish 21.2%; Middle Eastern 14.5%; Amish 32.1%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Cardiovascular & Metabolic
Heart Disease
Coronary Artery Disease. Evidence: 4/10. Source: PMID 19048183. Increased Risk.
Immunity & Inflammation
Infection Susceptibility & Resistance
Severe Malaria. Evidence: 3/10. Source: PMID 19055786. Typical Risk.
Inflammatory & Circulating Protein Markers
Soluble ICAM-1 Levels. Evidence: 10/10. Source: PMID 21533024. Higher Levels.
Organ Systems
Kidney Function & Disease
Diabetic Kidney Disease. Evidence: 3/10. Source: PMID 26255081. Typical Risk.
Showing effects for A/G genotype
Coronary Artery Disease. Evidence: 4/10. Source: PMID 19048183. Lower Risk.
Severe Malaria. Evidence: 3/10. Source: PMID 19055786. Increased Risk.
Soluble ICAM-1 Levels. Evidence: 10/10. Source: PMID 21533024. Lower Levels.
Diabetic Kidney Disease. Evidence: 3/10. Source: PMID 26255081. Lower Risk (Females).
Showing effects for G/G genotype
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Production of the reference form of the intercellular adhesion molecule 1 protein occurs in those with the A/A genotype, which is associated with higher circulating levels of soluble ICAM-1 [1]. Elevated levels of this adhesion molecule can promote vascular inflammation and the buildup of arterial plaque, increasing the risk of coronary artery disease [2]. Multiple clinical studies have linked this genotype to a higher likelihood of experiencing myocardial infarction or heart attacks [3]. On the other hand, this genotype appears to offer a typical baseline risk against severe malaria infections compared to those carrying the G allele [4]. For individuals with type 1 diabetes, this genetic profile is also associated with a standard baseline risk for developing kidney complications like diabetic nephropathy [5]. Maintaining a heart-healthy lifestyle through regular exercise and a balanced diet is particularly beneficial for managing cardiovascular risks associated with this profile.
Higher levels of circulating soluble ICAM-1; Increased susceptibility to coronary artery disease.
Sample genotype: AG (Heterozygous)
A balanced mixture of both the reference and variant forms of the adhesion molecule is produced in those with the A/G genotype, leading to moderately lower levels of soluble ICAM-1 in the blood [1]. This reduction in circulating adhesion molecules is associated with less vascular inflammation and a lower risk of developing coronary artery disease [2]. Clinical research suggests that individuals with this profile have a decreased susceptibility to heart attacks [3]. For females with type 1 diabetes, carrying this variant allele is also linked to a significantly reduced risk of developing diabetic nephropathy, a serious kidney complication [4]. However, this structural change in the adhesion receptor may slightly increase susceptibility to severe malaria in endemic regions, as the parasite can exploit these cell surface proteins [5]. Overall, this genetic profile provides a favorable cardiovascular outlook while maintaining a balanced immune response.
Lower levels of circulating soluble ICAM-1; Decreased risk of coronary artery disease; Reduced risk of diabetic nephropathy in females.
Sample genotype: GG (Homozygous)
Exclusive production of the variant form of intercellular adhesion molecule 1 occurs in those with the G/G genotype, resulting in the lowest levels of circulating soluble ICAM-1 [1]. This low level of adhesion molecules reduces the inflammatory recruitment of white blood cells to blood vessel walls, significantly lowering the risk of coronary artery disease [2]. Studies indicate that this profile is highly protective against myocardial infarction, commonly known as a heart attack [3]. Additionally, female patients with type 1 diabetes who carry this genotype experience a substantial reduction in their risk of developing diabetic nephropathy [4]. Despite these clear cardiovascular and renal benefits, the altered receptor structure is associated with an increased risk of severe malaria in regions where the disease is common [5]. This dual effect represents an evolutionary trade-off where a variant that protects the heart also influences infectious disease susceptibility.
Lowest levels of circulating soluble ICAM-1; Significantly decreased risk of coronary artery disease; Increased susceptibility to severe malaria in endemic regions.
Variants with shared genetic architecture
rs1799969 · ICAM1 Gene · Chr 19 · Breast Cancer Risk
rs3093030 · ICAM1 Gene · Chr 19 · Immune and Vascular Health
rs5491 · ICAM1 Gene · Chr 19 · Cerebral Malaria Risk
Content updated August 2026.
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