Neutrophil
Introduction
Section titled “Introduction”Neutrophils are a fundamental component of the human immune system, representing the most abundant type of white blood cell (WBC) in circulation. As granulocytes, they play a critical role in the innate immune response, acting as the body’s primary defense against bacterial and fungal infections.[1]The of neutrophil count is a routine part of a complete blood count (CBC) and serves as a vital indicator of overall health and disease states. Both genetic and environmental factors influence the number and size of cells in the blood.[2] and white blood cell counts, including neutrophils, are moderately heritable, with estimates varying across different cell subtypes.[3]
Biological Basis
Section titled “Biological Basis”Neutrophils are primarily produced in the bone marrow.[1]Their production, maturation, and migration are tightly regulated processes, involving various signaling molecules, including chemokines. Genetic variations can significantly impact neutrophil counts. A notable example is a regulatory variant in theDuffy antigen receptor for chemokines (DARC) gene, which is associated with lower neutrophil counts observed in individuals of African descent.[4]This variant is believed to alter the concentration and distribution of chemokines in the blood and tissues, thereby influencing neutrophil regulation.[5] Beyond DARC, genome-wide association studies (GWAS) have identified other loci associated with neutrophil count, such as common variations in thePSMD3-CSF3 and PLCB4 genes.[6] Additionally, the CDK6gene, which regulates cell progression and inhibits granulocytic differentiation, has variants linked to WBC and neutrophil counts.[5]
Clinical Relevance
Section titled “Clinical Relevance”The absolute neutrophil count (ANC) is a crucial diagnostic and prognostic marker. Abnormally low neutrophil counts, a condition known as neutropenia, can significantly increase an individual’s susceptibility to infections, particularly in immunocompromised patients or those undergoing treatments like chemotherapy.[5] Neutropenia can manifest in various forms, ranging from severe congenital neutropenia, which are rare monogenic disorders.[7] to benign ethnic neutropenia.[8]Conversely, elevated neutrophil counts, or neutrophilia, often indicate infection, inflammation, or other underlying medical conditions. Neutrophil counts are also associated with several cardiovascular disease risk factors, including higher blood pressure and cigarette smoking.[9]Understanding the genetic determinants of neutrophil levels can inform clinical strategies for managing conditions like cancer-associated neutropenia or optimizing hematopoietic stem cell mobilization.[5]
Social Importance
Section titled “Social Importance”Recognizing population-specific differences in neutrophil counts is vital for accurate diagnosis and appropriate medical care. For instance, the phenomenon of benign ethnic neutropenia, characterized by lower average neutrophil counts in individuals of African descent, is largely attributed to theDARC gene variant.[8]This genetic predisposition means that a neutrophil count considered low in a person of European ancestry might be within the normal range for someone of African descent. Failure to account for these ethnic variations can lead to misdiagnosis, unnecessary investigations, or inappropriate delays in critical treatments, such as chemotherapy, which often relies on specific neutrophil thresholds.[8] Studies have shown that the prevalence of neutropenia in the U.S. population varies by age, sex, smoking status, and ethnicity.[10]Advancing our understanding of the genetic and environmental factors influencing neutrophil counts therefore has significant implications for promoting personalized medicine and ensuring equitable healthcare practices globally.
Generalizability and Population Specificity
Section titled “Generalizability and Population Specificity”Neutrophil counts are known to vary significantly across different ancestral populations, posing challenges for the broad applicability of genetic findings. Research primarily focusing on specific populations, such as African Americans or Japanese individuals, may yield associations that do not directly generalize to other groups.[5] For instance, a variant like rs2814778 in the Duffy antigen receptor for chemokines gene, which significantly influences neutrophil counts in African Americans, is noted to be very rare in individuals of European ancestry.[11]This underscores the critical need for diverse cohorts to fully capture the genetic architecture of neutrophil traits globally.
Moreover, even when loci are identified across different ancestries, their effect sizes can differ substantially. Studies have shown that the impact of certain genetic variants on neutrophil counts can be considerably smaller in Caucasian populations compared to Japanese populations.[6] Such variations highlight the complex interplay of genetic backgrounds and population-specific allele frequencies, which can influence the clinical utility and interpretability of genetic associations across diverse demographics. These observations necessitate caution when extrapolating findings from one population to another without further validation.
Phenotypic and Confounding Factors
Section titled “Phenotypic and Confounding Factors”The accurate and consistent assessment of neutrophil counts is crucial, yet several factors can introduce variability. Phenotypic data, often collected from medical records or through self-report for clinical information, may be subject to inconsistencies or recall bias, potentially affecting the precision of associations.[5] Although studies employ standardized quality assurance procedures and automated cell counters, the process of blood collection (e.g., fasting samples) and subsequent data transformations (e.g., natural log or square-root) to normalize distributions can alter the direct interpretation of raw effect sizes.[5]Beyond , environmental and lifestyle factors represent significant confounders that are not always fully accounted for in genetic studies. Known influences such as smoking status have been shown to affect the prevalence of neutropenia, indicating a strong environmental component to neutrophil variation.[10]While some studies exclude individuals with certain conditions like cancer or AIDS at the time of blood count, the broader spectrum of environmental exposures and their complex interactions with genetic predispositions (gene-environment interactions) remains challenging to comprehensively assess, contributing to the unexplained variance in neutrophil counts.
Methodological and Statistical Considerations
Section titled “Methodological and Statistical Considerations”Despite the large sample sizes often employed in genome-wide association studies, certain methodological and statistical constraints can limit the scope and robustness of findings. For instance, while total white blood cell counts might be available for all participants, detailed subtype information, such as neutrophil counts, is frequently restricted to a smaller subset of individuals within a cohort.[5]This reduction in sample size can diminish statistical power for specific neutrophil associations, potentially leading to inflated effect sizes for identified variants or an inability to detect true associations with smaller effects.
Furthermore, issues such as genomic inflation factors, even if minor, can indicate subtle population stratification or other biases that may affect the reliability of p-values, as observed in some analyses where definitive causes could not be identified.[9] While meta-analyses combine data across studies to increase power, conservative exclusion criteria, such as those rejecting SNPs with high heterogeneity, might inadvertently exclude genuine associations that exhibit biological variability across different cohorts.[9]Finally, the fraction of variance explained by currently identified genetic loci for neutrophil counts is often modest, suggesting considerable “missing heritability” and highlighting the existence of numerous as-yet-undiscovered genetic and non-genetic factors influencing this trait.
Variants
Section titled “Variants”The genetic landscape influencing neutrophil measurements is complex, involving numerous genes that regulate immune responses, cellular development, and protein function. A significant cluster of variants is found within the defensin gene family, which includesDEFA1, DEFA3, DEFA4, DEFA5, DEFA6, and DEFA1B, alongside several pseudogenes like DEFT1P2, DEFA7P, DEFA9P, DEFA10P, and DEFA11P. Defensins are small, antimicrobial peptides crucial for the body’s innate immune system, primarily produced by neutrophils and specialized epithelial cells. These peptides combat pathogens by disrupting microbial membranes and modulating inflammatory signals. Variants such as rs149286471 , rs7459916 , rs2738058 , rs2738130 , rs2977813 , rs7825750 , rs4512398 , * Such genetic variations can directly impact the capacity of neutrophils to fight infections and regulate inflammation, potentially leading to observable differences in neutrophil counts or their functional state in blood tests. Pseudogenes, while not encoding functional proteins themselves, can influence the expression of their functional counterparts through various regulatory mechanisms, meaning variants likers118134834 , rs56177108 , and *rs62487513 * could indirectly modulate immune responses and neutrophil activity.[12] Another key gene involved in immune regulation is NLRP12, which encodes a protein vital for the innate immune system’s inflammasome pathway. NLRP12 acts as both a sensor for pathogen and danger signals and a negative regulator of inflammation, preventing excessive or prolonged immune responses that could Since neutrophils are central to acute inflammation and immune defense, modifications in NLRP12function due to these genetic variations could influence how neutrophils are recruited to sites of infection, how they become activated, and how long they survive, ultimately affecting their measured levels and the body’s overall inflammatory status. A disruption in the delicate balance of inflammasome activity, influenced by these variants, may contribute to chronic inflammatory conditions or aberrant immune responses, impacting the dynamic regulation of neutrophil populations.[12]Beyond direct immune effectors, genes involved in fundamental cellular processes also contribute to neutrophil characteristics. ThePSMD3 gene, for instance, codes for a subunit of the 26S proteasome, an essential cellular machine responsible for degrading damaged or unneeded proteins, a process critical for cell cycle progression, immune cell maturation, and stress responses. The variant rs3816472 in PSMD3might alter the efficiency of the proteasome, potentially affecting the turnover of proteins vital for neutrophil development or function. Similarly,TENT5A (also known as PAPD5) is a poly(A) RNA polymerase involved in modifying RNA molecules, thereby influencing gene expression. Variants like rs915125 and rs171835 in TENT5Acould impact RNA stability or the rate at which proteins are made, indirectly affecting the production of proteins crucial for neutrophil biology.[12] SNORA70, a small nucleolar RNA, is fundamental for proper ribosomal RNA modification and protein synthesis, suggesting that variations in this gene could have broad effects on cellular function, including in rapidly dividing immune cells like neutrophils. While GS1-24F4.2 is less understood, genetic variations such as rs2977799 , rs9772604 , an
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs149286471 rs7459916 | DEFA1B - DEFT1P2 | level of neutrophil defensin 1 (human) in blood neutrophil |
| rs2738058 rs118134834 | DEFA9P - DEFA10P | periodontitis IGA glomerulonephritis MANSC domain-containing protein 1 level of carcinoembryonic antigen-related cell adhesion molecule 6 in blood mitochondrial DNA |
| rs2738130 rs56177108 rs2977813 | DEFA10P - DEFA1 | neutrophil hematological |
| rs7825750 rs4512398 rs62487513 | DEFA3 - DEFA11P | neutrophil |
| rs62143206 rs111659207 rs34436714 | NLRP12 | granulocyte percentage of myeloid white cells monocyte percentage of leukocytes lymphocyte:monocyte ratio galectin-3 monocyte count |
| rs79350116 rs2741684 rs2738111 | DEFA6 - DEFA4 | neutrophil hematological |
| rs3816472 | PSMD3 | lymphocyte percentage of leukocytes neutrophil |
| rs13267464 rs11989117 rs149034020 | DEFA7P - DEFA5 | basophil percentage of leukocytes monocyte count monocyte percentage of leukocytes neutrophil hematological |
| rs915125 rs171835 | TENT5A - SNORA70 | granulocyte percentage of myeloid white cells monocyte percentage of leukocytes monocyte count lymphocyte:monocyte ratio DEFA1/LCN2 protein level ratio in blood |
| rs2977799 rs9772604 rs2951861 | GS1-24F4.2 | lymphocyte:monocyte ratio basophil count basophil percentage of leukocytes myeloblastin neutrophil |
Causes
Section titled “Causes”The circulating neutrophil count is a complex trait influenced by a confluence of genetic, environmental, and acquired factors, often exhibiting significant variation across individuals and populations. Understanding these causal elements is crucial for interpreting neutrophil levels in both healthy and disease states.
Genetic Architecture of Neutrophil Counts
Section titled “Genetic Architecture of Neutrophil Counts”Genetic factors play a substantial role in determining an individual’s neutrophil count, with heritability estimates for white blood cell counts, including neutrophils, ranging from approximately 14% to 60%.[5] Numerous inherited variants contribute to this variability, often in a polygenic manner, meaning multiple genes collectively influence the trait. For instance, genome-wide association studies (GWAS) have identified common polymorphisms in regions such as the PSMD3-CSF3 locus and the CDK6gene as significantly associated with neutrophil counts in diverse populations, including those of European and Japanese descent.[13] The PSMD3 gene, through its role in proteasome function, and CDK6, which inhibits terminal granulocytic differentiation, represent plausible biological mechanisms by which these genetic variations modulate neutrophil production and maturation.[9]Furthermore, specific genetic variants can lead to more pronounced, sometimes monogenic, alterations in neutrophil levels, such as the rare inherited forms of severe congenital neutropenia.[7] A notable example of a common genetic variant with a significant impact is a regulatory polymorphism in the DARC(Duffy antigen receptor for chemokines) gene, which is largely responsible for the substantially lower neutrophil counts observed in individuals of African descent compared to those of European ancestry.[8] This DARCvariant, which abolishes expression of the receptor on red blood cells, is thought to alter chemokine concentrations and distribution, thereby influencing neutrophil production and migration.[5]This single variant alone can account for approximately 20% of the total variation in neutrophil counts within certain populations.[9]
Environmental, Lifestyle, and Demographic Influences
Section titled “Environmental, Lifestyle, and Demographic Influences”Beyond genetics, a range of environmental and lifestyle factors contribute to variations in neutrophil counts. Demographic characteristics such as age, sex, and ethnicity are known to influence neutrophil levels, with studies reporting differences in the prevalence of neutropenia across these groups.[10]Lifestyle choices, particularly cigarette smoking, are directly associated with higher white blood cell counts, including neutrophils.[10]Socioeconomic status also plays a role, with lower socioeconomic status correlating with higher leukocyte counts.[9] Geographic and environmental exposures can also exert an influence. The prevalence of certain genetic variants, such as the DARCnull allele, is higher in populations from regions where malaria is endemic, suggesting a selective advantage and thereby linking geographic influences to neutrophil regulation.[9]The broader impact of lifestyle and environmental exposures underscores the dynamic interplay between an individual and their surroundings in shaping their neutrophil profile.
Gene-Environment Interactions and Acquired Conditions
Section titled “Gene-Environment Interactions and Acquired Conditions”Neutrophil counts are also shaped by intricate gene-environment interactions and various acquired conditions. A prominent example of gene-environment interaction is theDARCgene variant, which, while leading to lower neutrophil counts, also confers a selective advantage against malaria, particularly in sub-Saharan African populations where the variant is nearly fixed in frequency.[9] This illustrates how genetic predispositions can interact with environmental pressures (like infectious diseases) to influence physiological traits.
Furthermore, several acquired conditions and external factors can significantly alter neutrophil levels. Comorbidities, such as cardiovascular disease risk factors like higher blood pressure and adiposity, are associated with elevated total white blood cell counts, often implicating neutrophils.[9]Medications, particularly chemotherapy, are well-known to induce neutropenia, necessitating careful monitoring and sometimes adjustments to treatment protocols based on neutrophil levels.[10]These factors highlight that neutrophil levels are not static but are dynamically regulated by a combination of inherent genetic makeup, environmental exposures, and an individual’s health status.
Neutrophil Biology and Homeostasis
Section titled “Neutrophil Biology and Homeostasis”Neutrophils are a critical component of the innate immune system, functioning as essential white blood cells (WBCs) that defend the body against invading microorganisms. These cells are one of five main WBC subtypes, each playing diverse roles in immune responses.[6]The precise regulation of neutrophil numbers circulating in peripheral blood is crucial, as any abnormality in their count is closely linked to various disease states and systemic health disruptions.[6]The overall stability of neutrophil levels, known as homeostasis, is a tightly controlled biological process.[14]This delicate balance involves complex interactions between genetic predisposition and environmental factors, which collectively influence both the size and quantity of blood cells.[2]Neutrophil counts are also moderately heritable, with genetic factors contributing significantly to individual variations, highlighting the importance of understanding both intrinsic and extrinsic regulators of their biology.[9]
Molecular Regulation of Neutrophil Development and Trafficking
Section titled “Molecular Regulation of Neutrophil Development and Trafficking”The life cycle and movement of neutrophils are orchestrated by intricate molecular and cellular pathways involving key biomolecules. Hematopoietic cytokines, such as G-CSF(Granulocyte-colony stimulating factor), are fundamental regulators, particularly in governing neutrophil trafficking from the bone marrow, where they are produced, into the bloodstream.[1], [15] This mobilization is a coordinated effort, often involving G-CSF alongside ELR+CXCchemokines, which together facilitate neutrophil egress during acute inflammatory responses.[16] Further regulatory complexity is seen in the antagonistic roles of chemokine receptors CXCR2 and CXCR4, which finely tune neutrophil trafficking from the bone marrow.[17] Signaling pathways are also crucial, with the STAT3transcription factor playing a pivotal role in controlling the neutrophil migratory response toCXCR2 ligands; STAT3 achieves this by directly activating G-CSF-induced CXCR2 expression and modulating its downstream signal transduction.[18] Additionally, the CDK6 (cyclin-dependent kinase 6) gene, which regulates cell progression in proliferating hematopoietic progenitor cells, interacts with the transcription factor Runx1to inhibit the terminal differentiation of granulocytes, thereby influencing neutrophil maturation.[5] The PSMD3gene, encoding a subunit of the 26S proteasome, also plays a role in cell cycle regulation via the ubiquitin–proteasome pathway, with its expression being associated with neutrophil count variations.[5]
Genetic Influences on Neutrophil Count
Section titled “Genetic Influences on Neutrophil Count”Genetic mechanisms significantly contribute to the variation in neutrophil counts within populations. The heritability of totalWBC count and its subtypes, including neutrophils, is estimated to range from approximately 14% to 40%.[9] A notable genetic determinant is a regulatory variant in the DARC(Duffy Antigen Receptor for Chemokines) gene, which accounts for approximately 20% of the variation in neutrophil and totalWBC counts, particularly in individuals of African descent.[4], [9] This Duffy null variant abolishes DARCexpression on red blood cells, which in turn can alter the concentration and distribution of chemokines in the blood and tissues, thereby influencing neutrophil production and migration.[5] Beyond DARC, genome-wide association studies (GWAS) have identified several other loci associated with neutrophil counts. Common polymorphisms residing in the 17q21 region, which harbors theCSF3 gene, have been linked to circulating total WBC and WBC subtype counts in various populations.[5], [6] Specific genes like PSMD3-CSF3 and PLCB4are associated with neutrophil count.[6] Expression Quantitative Trait Loci (eQTL) analyses indicate that genetic variants near PSMD3-CSF3 influence PSMD3 expression, rather than CSF3itself, impacting neutrophil variation.[5] Furthermore, the rs445 variant within the CDK6 gene on chromosome 7 has been identified as a lead SNP associated with WBCcount in both Japanese and African American populations, highlighting its potential role as a causal variant affecting neutrophil biology.[5]
Pathophysiological Implications of Neutrophil Dysregulation
Section titled “Pathophysiological Implications of Neutrophil Dysregulation”Disruptions in neutrophil counts can have significant pathophysiological consequences, ranging from benign conditions to severe disease states. Benign ethnic neutropenia (BEN), for instance, is characterized by a lower absolute neutrophil count that is more prevalent in certain ethnic groups, such as individuals of African descent, partly due to theDARC gene variant.[4], [8], [10]Beyond benign variations, abnormalities in neutrophil numbers are closely linked to overall immune system function and susceptibility to various diseases.[6]Severe congenital neutropenia represents a group of rare, inherited monogenic disorders characterized by extremely low neutrophil counts, underscoring the critical role of genetic integrity in neutrophil development.[7] On a broader systemic level, total WBCcount, which is heavily influenced by neutrophils, is directly associated with cardiovascular disease risk factors such as higher blood pressure, cigarette smoking, adiposity, and elevated plasma inflammatory markers.[9]Understanding the genetic and molecular underpinnings of neutrophil variation can therefore inform clinical approaches, particularly in managing conditions like cancer-associated neutropenia or optimizing hematopoietic stem cell mobilization for therapeutic purposes.[5]
Diagnostic and Prognostic Indicator in Systemic Conditions
Section titled “Diagnostic and Prognostic Indicator in Systemic Conditions”Neutrophil count, a key component of the white blood cell (WBC) differential, serves as a fundamental clinical measure reflecting the body’s immune and inflammatory status.[9]Elevated neutrophil counts, even when within the clinically designated normal range, are consistently associated with an increased risk of coronary artery disease, certain cancers, and overall mortality.[9]These associations are further supported by correlations with established cardiovascular disease risk factors such as higher blood pressure, cigarette smoking, adiposity, lower socioeconomic status, and elevated plasma inflammatory markers, making neutrophil levels a valuable tool for risk stratification and identifying individuals at higher risk for these systemic conditions.[9]Beyond general risk assessment, neutrophil levels also carry significant prognostic value, informing predictions of disease progression and long-term outcomes. For instance, in patients undergoing treatment for chronic hepatitis C, the absolute neutrophil count (ANC) is closely monitored, with quantitative changes at specific time points, such as week 4, analyzed to understand treatment-induced cytopenia.[19]This monitoring helps assess treatment response and can influence decisions regarding dose modifications of pegylated interferon (pegIFN) and ribavirin (RBV) or the use of erythropoietin supplementation, thereby guiding personalized medicine approaches and improving patient care.[19]
Genetic and Population-Specific Considerations in Neutropenia
Section titled “Genetic and Population-Specific Considerations in Neutropenia”Neutrophil counts exhibit notable variations across different populations, most notably the phenomenon of benign ethnic neutropenia (BEN), characterized by persistently lower absolute neutrophil counts in individuals of African descent compared to those of European ancestry.[8] This genetic predisposition is partly attributed to a regulatory variant in the Duffy Antigen Receptor for Chemokines (DARC) gene, which accounts for approximately 20% of the total variation in neutrophil measures within these populations.[4] Recognizing BEN is crucial for accurate diagnosis, preventing the misattribution of a physiological trait to a pathological condition, and avoiding unnecessary diagnostic workups or interventions, thereby emphasizing the need for population-specific reference ranges in clinical practice.[8]The genetic underpinnings of neutrophil levels extend to informing clinical management in various other scenarios, including cancer-associated neutropenia and hematopoietic stem cell mobilization.[5]Studies have investigated the feasibility of lowering the target neutrophil cutoff for initiating or resuming chemotherapy in African Americans with BEN, suggesting a more personalized approach to managing treatment-induced cytopenia based on genetic background.[10] Furthermore, the identification of genetic variants in loci such as _PSMD3-CSF3_ (rs4794822 ) and _CDK6_ (rs445 ) that influence neutrophil counts could contribute to enhanced risk stratification and more precise treatment selection in conditions where neutrophil levels are a critical determinant of patient outcomes.[20]
Frequently Asked Questions About Neutrophil
Section titled “Frequently Asked Questions About Neutrophil”These questions address the most important and specific aspects of neutrophil based on current genetic research.
1. Is my “normal” neutrophil count different because of my ancestry?
Section titled “1. Is my “normal” neutrophil count different because of my ancestry?”Yes, absolutely. For example, if you are of African descent, your “normal” neutrophil count might naturally be lower than someone of European ancestry. This is largely due to a common variant in theDARC gene, which is prevalent in people of African descent. Doctors need to consider your ethnic background to avoid misinterpreting your blood test results.
2. Will my kids inherit my low neutrophil counts?
Section titled “2. Will my kids inherit my low neutrophil counts?”There’s a good chance. Neutrophil counts are moderately heritable, meaning they can be passed down in families. If you or your partner have genetic variations, like in theDARC gene, that lead to lower counts, your children could inherit those tendencies. However, environmental factors also play a role.
3. Am I more prone to infections if my neutrophils are low?
Section titled “3. Am I more prone to infections if my neutrophils are low?”Yes, definitely. Low neutrophil counts, a condition called neutropenia, can significantly increase your risk of getting infections, especially bacterial and fungal ones. Neutrophils are your body’s primary defense against these invaders, so fewer of them mean less protection.
4. Does smoking affect how many neutrophils I have?
Section titled “4. Does smoking affect how many neutrophils I have?”Yes, your lifestyle choices, like smoking, can influence your neutrophil counts. Studies have shown a connection between cigarette smoking and certain cardiovascular risk factors, which include effects on your white blood cell phenotypes, like neutrophil levels.
5. Could my doctor misinterpret my neutrophil count if I’m of African descent?
Section titled “5. Could my doctor misinterpret my neutrophil count if I’m of African descent?”Unfortunately, yes, it’s a known issue. If your doctor isn’t aware of benign ethnic neutropenia, which is common in people of African descent due to the DARC gene variant, they might mistakenly think your naturally lower count is a problem. This could lead to unnecessary tests or even delays in crucial treatments like chemotherapy.
6. Why does my doctor care so much about my neutrophil levels during treatment?
Section titled “6. Why does my doctor care so much about my neutrophil levels during treatment?”Your neutrophil levels are crucial because many treatments, especially chemotherapy, can severely lower them. When your neutrophils are too low (neutropenia), your immune system is compromised, putting you at a much higher risk of life-threatening infections. Doctors monitor these counts closely to ensure your safety during treatment.
7. Are high neutrophils always a sign I’m sick or inflamed?
Section titled “7. Are high neutrophils always a sign I’m sick or inflamed?”Elevated neutrophil counts, or neutrophilia, often indicate an underlying issue like an infection or inflammation in your body. While not always a sign of severe illness, it usually means your immune system is actively responding to something.
8. Why are my neutrophil numbers different from my friends’?
Section titled “8. Why are my neutrophil numbers different from my friends’?”Your neutrophil numbers can differ from others due to a mix of genetic and environmental factors. We all have unique genetic makeups, with variants in genes likeDARC, PSMD3-CSF3, PLCB4, or CDK6influencing our individual counts. Plus, lifestyle and health conditions also play a role.
9. Can my neutrophil levels impact my risk for heart problems?
Section titled “9. Can my neutrophil levels impact my risk for heart problems?”Yes, there’s an association. Neutrophil counts are linked to several cardiovascular disease risk factors, including higher blood pressure. Monitoring your neutrophil levels can provide insights into your overall health and potential risks beyond just infection.
10. Is a DNA test useful to understand my neutrophil levels better?
Section titled “10. Is a DNA test useful to understand my neutrophil levels better?”Yes, a DNA test could be quite informative. Genetic variations, such as those in the DARCgene or other loci identified by studies, significantly influence neutrophil counts. Understanding your genetic predispositions can help you and your doctor interpret your routine blood tests more accurately and personalize your care.
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] Metcalf, D. “Hematopoietic Cytokines.” Blood, vol. 111, 2008, pp. 485–491.
[2] Whitfield, J. B., and N. G. Martin. “Genetic and Environmental Influences on the Size and Number of Cells in the Blood.”Genet Epidemiol, vol. 2, 1985, pp. 133–144.
[3] Pilia, G., W. M. Chen, A. Scuteri, M. Orru, G. Albai, et al. “Heritability of Cardiovascular and Personality Traits in 6,148 Sardinians.”PLoS Genet, vol. 2, 2006, p. e132.
[4] Reich, D., et al. “Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene.”PLoS Genetics, vol. 5, no. 1, 2009, e1000360.
[5] Reiner, A. P., et al. “Genome-Wide Association Study of White Blood Cell Count in 16,388 African Americans: The Continental Origins and Genetic Epidemiology Network (COGENT).” PLoS Genet, vol. 7, no. 6, 2011, p. e1002108.
[6] Okada, Y., et al. “Identification of Nine Novel Loci Associated with White Blood Cell Subtypes in a Japanese Population.” PLoS Genet, vol. 7, no. 6, 2011, p. e1002067.
[7] Dale, D. C., and D. C. Link. “The Many Causes of Severe Congenital Neutropenia.” N Engl J Med, vol. 360, 2009, pp. 3–5.
[8] Haddy, T. B., et al. “Benign Ethnic Neutropenia: What Is a Normal Absolute Neutrophil Count?”Journal of Laboratory and Clinical Medicine, vol. 133, 1999, pp. 15–22.
[9] Nalls, M. A., et al. “Multiple Loci Are Associated with White Blood Cell Phenotypes.” PLoS Genet, vol. 7, no. 6, 2011, p. e1002020.
[10] Hsieh, M. M., et al. “Neutrophil count in African Americans: lowering the target cutoff to initiate or resume chemotherapy?”Journal of Clinical Oncology, vol. 28, no. 10, 2010, pp. 1633-1637.
[11] Crosslin, David R., et al. “Genetic variants associated with the white blood cell count in 13,923 subjects in the eMERGE Network.” Hum Genet.
[12] Melzer D. “A genome-wide association study identifies protein quantitative trait loci (pQTLs).” PLoS Genet, vol. 4, no. 5, May 2008, p. e1000072.
[13] Soranzo, Nicole, et al. “A Genome-Wide Meta-Analysis Identifies 22 Loci Associated with Eight Hematological Parameters in the HaemGen Consortium.”Nature Genetics, vol. 41, 2009, pp. 1182–1190.
[14] Christopher, M. J., and D. C. Link. “Regulation of Neutrophil Homeostasis.”Current Opinion in Hematology, Jan. 2007, pp. 3–8.
[15] Semerad, C. L., et al. “G-CSFIs an Essential Regulator of Neutrophil Trafficking from the Bone Marrow to the Blood.”Immunity, vol. 17, 2002, pp. 413–23.
[16] Wengner, A. M., et al. “The Coordinated Action of G-CSF and ELR+CXCChemokines in Neutrophil Mobilization During Acute Inflammation.”Blood, vol. 111, 2008, pp. 42–49.
[17] Eash, K. J., et al. “CXCR2 and CXCR4Antagonistically Regulate Neutrophil Trafficking from Murine Bone Marrow.”Journal of Clinical Investigation, vol. 120, 2010, pp. 2423–31.
[18] Nguyen-Jackson, H., et al. “STAT3Controls the Neutrophil Migratory Response toCXCR2 Ligands by Direct Activation of G-CSF-Induced CXCR2 Expression and Via Modulation of CXCR2 Signal Transduction.” Blood, vol. 115, 2010, pp. 3354–63.
[19] Thompson, A. J., et al. “Genome-Wide Association Study of Interferon-Related Cytopenia in Chronic Hepatitis C Patients.”J Hepatol, vol. 55, no. 6, 2011, pp. 1210–1218.
[20] Okada, Y., et al. “Common Variations in PSMD3-CSF3 and PLCB4Are Associated with Neutrophil Count.”Human Molecular Genetics, vol. 19, 2010, pp. 2079–2085.