Eotaxin
Introduction
Section titled “Introduction”Eotaxin, also known as CCL11 (CCL11), is a chemokine, a type of signaling protein that plays a crucial role in the immune system. It is primarily recognized for its ability to selectively recruit eosinophils, a specific type of white blood cell, to sites of inflammation. This targeted recruitment is a key component of the body’s response to allergens, parasites, and certain inflammatory diseases. Understanding the factors that influence circulating eotaxin levels is vital for elucidating disease mechanisms and identifying potential therapeutic avenues.
Biological Basis
Section titled “Biological Basis”Eotaxin (CCL11) is a small cytokine that belongs to the CC chemokine family. Its primary function is to act as a chemoattractant for eosinophils, guiding them through the bloodstream to specific tissues where they are needed to combat pathogens or contribute to allergic reactions. Genetic variations can significantly influence an individual’s circulating eotaxin levels. For instance, the single nucleotide polymorphism (SNP)rs12075 at chromosome 1q23.2 is strongly associated with eotaxin levels.[1] This variant is located within ACKR1 (Atypical Chemokine Receptor 1), a gene encoding a receptor known to bind multiple cytokines.[1] Research suggests that the impact of rs12075 on eotaxin levels is mediated by an alteration in how eotaxin binds to theACKR1 receptor.[1] Similarly, rs2228467 at 3p22.1 also influences eotaxin levels, with its effect appearing to be mediated viaACKR2 (Atypical Chemokine Receptor 2).[1] While eQTL (expression Quantitative Trait Loci) data for CCL11 in blood have not always been robustly available, studies continue to explore the intricate genetic regulation of this important chemokine.[2]
Clinical Relevance
Section titled “Clinical Relevance”The levels of circulating eotaxin are clinically relevant due to its central role in inflammatory and allergic responses. Elevated eotaxin levels are often observed in conditions such as asthma, allergic rhinitis, and other eosinophil-driven inflammatory diseases. Genetic studies, particularly protein quantitative trait loci (pQTL) analyses, aim to identify genetic variants that influence plasma protein levels, including eotaxin.[3], [4], [5]By linking specific genetic variations to eotaxin abundance, researchers can uncover genetic drivers of immune-mediated disease risk and identify novel therapeutic targets.[2]These genetic insights can help explain individual differences in disease susceptibility and progression, offering pathways for more personalized medical interventions.[1]
Social Importance
Section titled “Social Importance”Understanding the genetic underpinnings of eotaxin levels carries significant social importance. It contributes to a deeper knowledge of the genetic architecture of inflammatory diseases, which affect a large portion of the global population. This knowledge can facilitate the development of more effective diagnostic tools and targeted treatments, potentially reducing the burden of chronic inflammatory conditions. Large-scale genetic studies, often involving diverse populations such as those of European ancestry.[2] and Black adults.[5] and utilizing extensive datasets like the UK Biobank.[3] exemplify a collaborative scientific effort. This approach promotes data sharing and accelerates discoveries that can lead to advancements in personalized medicine, allowing for tailored prevention strategies and therapies based on an individual’s genetic profile.
Methodological and Statistical Considerations
Section titled “Methodological and Statistical Considerations”The studies investigating eotaxin levels primarily employ observational designs, such as genome-wide association studies (GWAS) and exome-wide association studies (ExWAS).[3] This inherent characteristic means that experimental randomization and blinding, which are fundamental for establishing causality, were not applicable to these investigations.[3]Consequently, while these studies can identify robust associations between genetic variants and eotaxin levels, directly inferring causal relationships is challenging due to the potential influence of unmeasured confounding factors. Furthermore, despite efforts to achieve large sample sizes, particularly through meta-analyses, formal power calculations were not consistently performed to determine sample size for discovery studies.[2] Rigorous statistical significance thresholds, such as P ≤ 5 × 10−10 with Bonferroni correction for multiple proteins or P ≤ 1 × 10−8 for ExWAS, were applied to control for false positives.[3] However, some analytical methods, like REGENIE, exhibited inflated test statistics in datasets with high levels of relatedness, underscoring the necessity for meticulous calibration checks to ensure the robustness of findings.[6] Replication across independent cohorts, while crucial for validating associations, can be influenced by variations in study designs, specific variant filtering criteria, and the choice of GWAS methods, potentially leading to inconsistencies in reported associations.[6] The presence of intercohort heterogeneity, even after applying strict criteria for meta-analysis inclusion and significance, also highlights the complexity of combining diverse datasets.[2]
Generalizability and Phenotypic Accuracy
Section titled “Generalizability and Phenotypic Accuracy”A significant limitation in understanding the genetics of eotaxin is the predominant focus on populations of European ancestry in many of the foundational studies.[3] For instance, analyses within large cohorts like the UK Biobank often restricted participants to those of European ancestry, and some meta-analyses explicitly filtered results to European-ancestry populations.[3] While some research has included individuals from other ancestries, such as Black adults, protein measurements were frequently residualized on race and genetic principal components, which might inadvertently obscure unique ancestry-specific genetic effects or interactions.[5]This narrow ancestral scope limits the direct generalizability of genetic findings for eotaxin levels to other global populations, where genetic architectures, allele frequencies, linkage disequilibrium patterns, and environmental exposures can differ considerably.
The accuracy and consistency of eotaxin measurements are also dependent on the specific assay platforms utilized, such as SOMAscan and Olink.[3] While internal quality control measures, including coefficients of variation and correlations between assays, generally demonstrate good reliability.[4] the antibody-based nature of platforms like Olink introduces a potential for “epitope effects.” These effects occur when genetic variants within or near antibody binding sites could directly interfere with protein quantification, thereby measuring an artifact of the assay rather than true protein abundance.[3]Although this concern has been acknowledged, comprehensive data to systematically assess such epitope effects, by testing overlap with known antibody binding sites, were not available for analysis. Furthermore, varying data exclusion criteria (e.g., minor allele frequency, imputation quality, Hardy-Weinberg equilibrium) and standardization procedures (e.g., log transformation, residualization for covariates like age, sex, batch, and principal components, and inverse normalization) were applied across different studies, which, while necessary for robust analysis, could introduce subtle heterogeneity in the measured eotaxin phenotype across cohorts.[5]
Confounding Factors and Unexplained Variance
Section titled “Confounding Factors and Unexplained Variance”The observational design of these studies makes it challenging to fully account for the intricate interplay between genetic factors and environmental exposures, or complex gene-environment interactions, that influence eotaxin levels. Although comprehensive covariate adjustments were made, including factors like age, sex, smoking status, body mass index, assessment center, collection site, batch, and the time difference between blood sampling and protein , along with genetic principal components.[3]unmeasured environmental factors or lifestyle choices could still confound observed genetic associations. This inherent limitation makes it difficult to conclusively distinguish direct genetic effects from those that are modulated by environmental influences, potentially leading to an incomplete understanding of eotaxin’s regulation and biological pathways.
Despite significant progress in identifying genetic variants associated with eotaxin levels, a notable portion of the heritability for this trait remains unexplained, a phenomenon often referred to as “missing heritability”.[5]This suggests that current genetic models may not fully capture the contributions of various factors, including rare variants, structural variations, epigenetic modifications, or complex gene-gene and gene-environment interactions that contribute to eotaxin variation. Moreover, while computational tools like ProGeM are utilized to prioritize probable mediating genes at trans-pQTLs and colocalization analyses help identify cis-expression quantitative trait loci (_eQTL_s), the precise causal mechanisms linking identified genetic variants to changes in eotaxin levels are not always fully elucidated.[2]Continued research is necessary to address these remaining knowledge gaps, move beyond purely correlational findings, and provide a more comprehensive understanding of the genetic and environmental architecture underlying eotaxin biology.
Variants
Section titled “Variants”Variants impacting the expression and function of chemokine receptors and other immune-related genes play significant roles in modulating circulating eotaxin levels, a key mediator in allergic inflammation. The atypical chemokine receptorsACKR1 and ACKR2 are central to this regulation. For instance, the variant rs12075 , located within the ACKR1gene at chromosome 1q23.2, is strongly associated with increased concentrations of eotaxin, monocyte chemotactic protein-1 (MCP1), and growth-regulated oncogene-alpha (GROa) in circulation. This association is thought to arise from altered binding of these chemokines to theACKR1 receptor, which acts as a scavenger to remove them from the bloodstream . Before analysis, these transformed protein levels are meticulously adjusted for various demographic and technical covariates, including age, sex, and duration between blood draw and processing, often incorporating principal components of ancestry to account for genetic stratification.[1], [4] Different biological matrices are utilized for quantification, with studies reporting measurements from EDTA plasma, heparin plasma, or serum, each potentially influencing the observed protein levels.[1] The resulting protein residuals, after covariate adjustment, are frequently rank-inverse normalized to ensure a robust, normally distributed phenotype for subsequent genetic association testing.[1], [4]
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs2228467 rs3919627 rs62247910 | ACKR2, CYP8B1 | granulocyte percentage of myeloid white cells monocyte percentage of leukocytes eosinophil percentage of leukocytes eosinophil count eosinophil percentage of granulocytes |
| rs10808297 rs10755885 rs6467885 | CCL24 - RHBDD2 | eotaxin C-C motif chemokine 13 level basophil |
| rs140905292 rs9903369 | LINC01989 | eotaxin |
| rs12075 rs2814778 | ACKR1, CADM3-AS1 | basophil count C-C motif chemokine 2 level leukocyte quantity self reported educational attainment monocyte count |
| rs3181077 rs1491961 | CCR3 | basophil count narcolepsy-cataplexy syndrome basophil percentage of leukocytes basophil percentage of granulocytes eotaxin |
| rs4683346 | ACKR2 | granulocyte percentage of myeloid white cells eotaxin |
| rs4076251 | LINC01228 - DYNLRB2-AS1 | eotaxin |
| rs34004101 rs115333627 | CCDC13 | eotaxin C-C motif chemokine 24 monocyte count monocyte percentage of leukocytes |
| rs892090 | GP6, GP6-AS1 | eotaxin C-C motif chemokine 13 level CD63 antigen transforming growth factor beta-1 amount amount of arylsulfatase B (human) in blood |
| rs7896518 | JMJD1C | platelet count neutrophil count, basophil count myeloid leukocyte count intelligence intelligence, self reported educational attainment |
Statistical Modeling and Adjustment Criteria
Section titled “Statistical Modeling and Adjustment Criteria”In the context of genetic studies, circulating protein levels are treated as quantitative traits, modeled as a combination of fixed and random effects to account for both genetic and environmental influences.[6]This involves linear regression models, often incorporating a comprehensive set of non-genetic factors as covariates, such as lifestyle, environmental exposures, medical history variables, and blood cell counts.[7] A linear mixed model may be employed to further correct protein expression levels for specific covariates and kinship, using a genetic relationship matrix to address population structure.[7] These rigorous adjustment protocols are critical for isolating the genetic contribution to protein variability and preventing spurious associations.
Genetic Association Terminology and Significance Thresholds
Section titled “Genetic Association Terminology and Significance Thresholds”The study of genetic influences on circulating protein levels involves specific terminology and stringent diagnostic and criteria. A key term is “protein quantitative trait locus” (pQTL), which refers to a genetic variant associated with the abundance of a specific protein.[2], [8] These pQTLs are further classified as “cis-acting” if the associated genetic variant is located within a 1 megabase distance from the transcription start or end site of the gene encoding the protein, while all other associations are termed “trans-acting”.[7] Statistical significance for identifying pQTLs is typically defined by a conventional genome-wide significance threshold of P ≤ 5 × 10−8, which is often further adjusted via Bonferroni correction to P ≤ 5 × 10−10 when testing multiple proteins to account for the increased number of comparisons.[2] For meta-analysis results, additional criteria are applied to ensure robustness, requiring variants to be present in a minimum number of studies and participants, and mandating consistency in the direction of effect across studies, especially in the presence of heterogeneity.[2]
Quantification of Circulating Eotaxin Levels
Section titled “Quantification of Circulating Eotaxin Levels”The diagnosis or assessment of conditions involving eotaxin (CCL11) often begins with the precise quantification of its circulating levels in plasma. Immunoassay techniques are routinely employed for this purpose, offering robust methods for measuring various plasma proteins, including chemokines like eotaxin. Methods such as Luminex multi-analyte immunoassays (e.g., Discovery Map v3.3 from Myriad RBM) and Bio-Rad’s Bio-Plex Pro Human Cytokine assays are utilized to determine protein concentrations.[1] Additionally, the Olink Target-96 Inflammation immunoassay panel, which measures 91 inflammation-related proteins, provides Normalized Protein eXpression (NPX) as continuous data on a log2 scale.[2] These quantitative measurements are crucial for establishing baseline levels, identifying deviations that may indicate inflammatory or immune-mediated processes, and monitoring treatment efficacy.
Genetic and Molecular Profiling
Section titled “Genetic and Molecular Profiling”Genetic and molecular profiling offers a deeper understanding of the factors influencing eotaxin levels and their potential role in disease. Genome-wide association studies (GWAS) identify protein quantitative trait loci (pQTLs), which are genetic variants significantly associated with circulating protein concentrations.[1] These studies can pinpoint cis-pQTLs, where the genetic variant is located near the gene encoding the protein, or trans-pQTLs, where the variant is at a distant genomic location.[2] Further insights are gained through colocalization analyses of cis-pQTLs with cognate cis-expression quantitative trait loci (eQTLs) from databases like eQTLGen, the eQTL Catalogue, and GTEx v.8, which help determine if a shared causal variant affects both mRNA expression and protein abundance.[2] Rare variant associations with plasma protein levels can also be identified through whole-exome sequencing and collapsing analyses, aggregating variants within specific genes.[3] For comprehensive variant interpretation, tools like the Variant Effect Predictor (VEP) and databases such as DrugBank, MTR, REVEL, gnomAD, and ClinVar are used to annotate sentinel variants and their linkage disequilibrium proxies.[3]
Contextual Interpretation and Disease Association
Section titled “Contextual Interpretation and Disease Association”The clinical utility of eotaxin measurements extends beyond mere quantification to understanding its role in disease pathogenesis and identifying potential therapeutic targets. By correlating eotaxin levels and their genetic determinants with complex traits, researchers can explore whether specific cytokine concentrations contribute to disease development.[1] For instance, differential expression analysis of target genes, such as CXCL5(a chemokine similar to eotaxin), in patient cohorts (e.g., ulcerative colitis versus healthy donors) provides insights into disease-specific changes.[2]The integration of genetic associations with protein levels, along with comprehensive variant annotation and colocalization analyses, is vital for prioritizing potentially causal variants and understanding the regulatory mechanisms underlying protein abundance. This multifaceted approach aids in distinguishing the genetic and environmental influences on eotaxin levels, informing personalized medicine strategies and the development of targeted interventions for immune-mediated diseases.
Eotaxin: A Key Chemokine in Inflammatory Responses
Section titled “Eotaxin: A Key Chemokine in Inflammatory Responses”Eotaxin, also known asCCL11, is a critical cytokine involved in the body’s inflammatory processes. As a chemokine, eotaxin primarily functions to attract specific immune cells, particularly eosinophils, to sites of inflammation. Its presence in the circulating plasma is a measurable indicator of immune activity and can be assessed using various proteomic methods, such as the Olink Target-96 Inflammation immunoassay panel or Bio-Rad’s Bio-Plex Pro Human Cytokine assays.[1]Understanding the factors that influence eotaxin levels is crucial for unraveling the complexities of immune-mediated diseases and homeostatic disruptions.
Genetic Determinants of Circulating Eotaxin Levels
Section titled “Genetic Determinants of Circulating Eotaxin Levels”The concentration of eotaxin in circulation is significantly influenced by specific genetic mechanisms, with several loci identified through genome-wide association studies (GWAS) and protein quantitative trait loci (pQTL) analyses. For instance, the genetic variantrs12075 , located at chromosome 1q23.2, is strongly associated with circulating eotaxin levels.[1] Similarly, rs2228467 at 3p22.1 has been linked to variations in eotaxin concentrations.[1] These genetic associations highlight how inherited factors can modulate the body’s inflammatory protein profiles.
Role of Atypical Chemokine Receptors in Eotaxin Homeostasis
Section titled “Role of Atypical Chemokine Receptors in Eotaxin Homeostasis”A critical aspect of eotaxin regulation involves its interaction with atypical chemokine receptors. The effect ofrs12075 on eotaxin levels is attributed to altered binding of eotaxin to theACKR1 (Atypical Chemokine Receptor 1).[1] ACKR1, also known as the Duffy antigen receptor for chemokines, is a receptor for multiple cytokines and functions to scavenge chemokines, thereby regulating their availability in the extracellular environment rather than mediating traditional signaling. Likewise, the influence of rs2228467 on eotaxin appears to be mediated viaACKR2 (Atypical Chemokine Receptor 2), another receptor involved in sequestering chemokines.[1]These atypical receptors play a crucial role in maintaining chemokine homeostasis, impacting the systemic concentrations of inflammatory mediators like eotaxin.
Molecular and Cellular Pathways Regulating Eotaxin
Section titled “Molecular and Cellular Pathways Regulating Eotaxin”Genetic variants can exert their influence on eotaxin levels by affecting various molecular and cellular pathways. For example, variants likers12075 are located within the ACKR1gene, directly impacting the structure or expression of the receptor and consequently altering its binding affinity for eotaxin.[1] Such genetic changes can modify regulatory elements, affect transcription factor binding sites, or influence epigenetic modifications, ultimately leading to altered gene expression patterns and protein production. Colocalization analyses, which compare cis-pQTLs and cis-eQTLs, are used to identify shared causal variants that influence both mRNA expression and protein abundance, providing insight into the molecular mechanisms underlying protein level variations.[2] Although CCL11(eotaxin) itself has shown a lack of robust expression in blood in some eQTL studies, its circulating levels are clearly under genetic control, often mediated by regulatory proteins like its receptors.[2]
Eotaxin’s Systemic Impact and Immune Cell Context
Section titled “Eotaxin’s Systemic Impact and Immune Cell Context”Eotaxin’s presence in the plasma reflects systemic immune responses and has implications at the tissue and organ level. As a chemokine, eotaxin primarily influences immune cell trafficking, particularly of eosinophils, to sites of allergic inflammation or parasitic infections. The genetic regulation of circulating eotaxin levels, through mechanisms involving atypical chemokine receptors, demonstrates a sophisticated system for modulating immune cell recruitment and the overall inflammatory milieu.[1]Maintaining appropriate eotaxin concentrations is vital for immune function, as dysregulation can contribute to various pathophysiological processes, including allergic diseases and other immune-mediated conditions. The broader context of circulating inflammatory proteins, including other chemokines likeCCL17 which mediates inflammation via IRF4.[9] underscores the interconnectedness of these biomolecules in orchestrating immune responses throughout the body.
Genetic and Transcriptional Regulation of Eotaxin
Section titled “Genetic and Transcriptional Regulation of Eotaxin”The circulating levels of eotaxin, also known asCCL11, are subject to intricate genetic and regulatory control mechanisms. Genetic variations, specifically protein quantitative trait loci (pQTLs), play a significant role in determining the abundance of proteins in plasma. For instance, the single nucleotide polymorphismrs2228467 , located at chromosome 3p22.1, has been identified as influencing eotaxin concentrations.[1] This genetic variant is thought to mediate its effect through the atypical chemokine receptor 2 (ACKR2), highlighting a direct link between genetic predisposition and protein levels. While cis-eQTLs (expression quantitative trait loci) are crucial for many genes, studies have noted that CCL11(eotaxin) may not always exhibit robust cis-eQTL associations in certain tissues like blood, suggesting that post-transcriptional or other regulatory layers might be particularly influential in determining its final protein abundance.[2]
Chemokine Receptor Interaction and Signaling Modulation
Section titled “Chemokine Receptor Interaction and Signaling Modulation”Eotaxin exerts its biological effects primarily through interaction with specific chemokine receptors, and its levels are critically modulated by chemokine-binding proteins. The genetic variantrs2228467 influences eotaxin concentrations by affecting the atypical chemokine receptor 2 (ACKR2).[1] ACKR2is a non-signaling receptor that acts as a “scavenger” for various inflammatory chemokines, including eotaxin, by internalizing and degrading them, thereby regulating their local concentrations and preventing excessive inflammation. This mechanism represents a crucial regulatory feedback loop, whereACKR2controls the availability of eotaxin to its cognate signaling receptors, thus influencing downstream cellular responses such as immune cell trafficking and activation. The functional significance of this interaction lies in its ability to finely tune the inflammatory milieu, preventing both insufficient and overactive immune responses.
Post-Translational Regulation and Functional Availability
Section titled “Post-Translational Regulation and Functional Availability”Beyond direct gene expression, the functional availability of eotaxin is also shaped by various post-translational and protein-level regulatory mechanisms. The regulation of circulating eotaxin levels, particularly as influenced by genetic variants likers2228467 and its interaction with ACKR2, directly impacts the amount of bioactive protein present. ACKR2’s role as a chemokine scavenger actively reduces the concentration of eotaxin in the extracellular space, effectively modulating its ability to bind to and activate traditional signaling receptors. This continuous modulation of protein abundance and localization represents a critical form of post-translational control, ensuring that eotaxin’s potent inflammatory and chemotactic signals are tightly controlled and precisely targeted within the physiological system.
Disease Relevance and Therapeutic Targets
Section titled “Disease Relevance and Therapeutic Targets”Dysregulation in the pathways governing eotaxin levels can have significant implications for various immune-mediated diseases. Aberrant concentrations of eotaxin, whether due to genetic predispositions likers2228467 or altered ACKR2 function, can contribute to chronic inflammation or impaired immune responses. For instance, if ACKR2’s scavenging function is compromised, elevated eotaxin levels could perpetuate inflammatory conditions, whereas excessiveACKR2activity might dampen necessary immune responses. Understanding these mechanistic links, particularly the genetic factors influencing eotaxin-ACKR2 interactions, provides insights into potential therapeutic targets for immune-mediated diseases. ModulatingACKR2activity or directly targeting eotaxin pathways could offer strategies to restore immune homeostasis and mitigate disease progression.
Frequently Asked Questions About Eotaxin
Section titled “Frequently Asked Questions About Eotaxin”These questions address the most important and specific aspects of eotaxin based on current genetic research.
1. Why are my allergies worse than my friend’s?
Section titled “1. Why are my allergies worse than my friend’s?”Your individual genetic makeup can significantly influence your circulating levels of eotaxin, a key protein that recruits allergy-causing cells. Variants near genes likeACKR1 and ACKR2are known to affect how much eotaxin your body produces or processes. This can explain why some people have stronger allergic or inflammatory responses than others, even to the same triggers.
2. Will my kids get my bad allergies too?
Section titled “2. Will my kids get my bad allergies too?”Your children could inherit some of the genetic variations that influence your eotaxin levels and, consequently, your susceptibility to allergies. Research shows that specific genetic variants, such asrs12075 or rs2228467 , are associated with these levels, contributing to individual differences in immune responses. However, environmental factors and other genes also play a role, so it’s not a guarantee.
3. Does my family’s background affect my allergy risk?
Section titled “3. Does my family’s background affect my allergy risk?”Yes, your ancestral background can play a role. Many foundational studies on eotaxin levels have focused on people of European ancestry, and genetic architectures can differ across populations. This means that certain genetic influences on eotaxin levels, and thus allergy risk, might be unique or more prevalent in specific ethnic groups, like those of Black adults.
4. Could a special test tell me why my allergies are bad?
Section titled “4. Could a special test tell me why my allergies are bad?”A specialized genetic test, often called a pQTL analysis, could potentially identify genetic variants linked to your eotaxin levels. This information might help explain why your body has a stronger inflammatory response, as elevated eotaxin is seen in conditions like asthma and allergic rhinitis. It could offer insights into your personal disease susceptibility.
5. Can knowing my “allergy signals” help my treatment?
Section titled “5. Can knowing my “allergy signals” help my treatment?”Absolutely. Understanding the genetic factors that influence your eotaxin levels can help identify specific genetic drivers of your immune-mediated disease risk. This knowledge can lead to more personalized medical interventions, allowing doctors to tailor prevention strategies and therapies that might be more effective for your unique genetic profile.
6. Am I more prone to inflammation because of my genes?
Section titled “6. Am I more prone to inflammation because of my genes?”Yes, your genes can definitely make you more prone to inflammation. Eotaxin is a key signaling protein that recruits inflammatory cells, and your genetic variations influence its circulating levels. If you have variants associated with higher eotaxin, your body might have a more robust inflammatory response, contributing to conditions like asthma.
7. Why do some people get asthma, and others just sniffles?
Section titled “7. Why do some people get asthma, and others just sniffles?”This difference can be partly due to variations in eotaxin levels, which are influenced by genetics. Eotaxin (CCL11) is crucial for recruiting eosinophils, a type of white blood cell involved in allergic reactions and asthma. Genetic variants can make some individuals have higher eotaxin, leading to more severe, eosinophil-driven inflammatory diseases like asthma, while others experience milder symptoms.
8. Could a genetic test predict my future allergy problems?
Section titled “8. Could a genetic test predict my future allergy problems?”A genetic test identifying variants associated with eotaxin levels could provide insights into your genetic predisposition for immune-mediated diseases. By understanding these genetic drivers, researchers aim to predict individual differences in disease susceptibility and progression, potentially offering an early indication of future allergy or inflammatory conditions.
9. My sibling has mild allergies, but mine are awful; why?
Section titled “9. My sibling has mild allergies, but mine are awful; why?”Even within families, individual genetic variations can lead to significant differences in eotaxin levels. While you share many genes with your sibling, specific variants, likers12075 near ACKR1 or rs2228467 near ACKR2, could cause your body to have higher circulating eotaxin. This genetic difference can make your allergic responses much more severe than theirs.
10. Can I change my body’s allergic response if it’s genetic?
Section titled “10. Can I change my body’s allergic response if it’s genetic?”While genetics strongly influence your baseline eotaxin levels and allergic predisposition, understanding these influences can open doors to personalized interventions. Knowing your genetic drivers can help guide targeted therapies or prevention strategies. This doesn’t necessarily mean changing your genes, but rather managing their impact more effectively with tailored medical approaches.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
Section titled “References”[1] Ahola-Olli AV, et al. “Genome-wide Association Study Identifies 27 Loci Influencing Concentrations of Circulating Cytokines and Growth Factors.” Am J Hum Genet, 2016.
[2] Zhao JH, et al. “Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets.”Nat Immunol, 2023.
[3] Dhindsa, R. S., et al. “Rare variant associations with plasma protein levels in the UK Biobank.” Nature, 2023.
[4] Sun BB, et al. “Genomic atlas of the human plasma proteome.” Nature, 2018.
[5] Katz, D. H., et al. “Whole Genome Sequence Analysis of the Plasma Proteome in Black Adults Provides Novel Insights Into Cardiovascular Disease.”Circulation, 2021.
[6] Loya H, et al. “A scalable variational inference approach for increased mixed-model association power.” Nat Genet, 2024.
[7] Caron B, et al. “Integrative genetic and immune cell analysis of plasma proteins in healthy donors identifies novel associations involving primary immune deficiency genes.” Genome Med, 2022.
[8] Thareja G, et al. “Differences and commonalities in the genetic architecture of protein quantitative trait loci in European and Arab populations.” Hum Mol Genet, 2022.
[9] Achuthan, A., et al. “Granulocyte macrophage colony-stimulating factor induces CCL17 production via IRF4 to mediate inflammation.” Journal of Clinical Investigation, vol. 126, no. 9, 2016, pp. 3453–3466.