What causes wbc to be low
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Causes of Low White Blood Cell (WBC) Count
White blood cell (WBC) count is a critical clinical marker that can indicate various health conditions. A low WBC count, also known as leukopenia, can be caused by several factors, including genetic predispositions, lifestyle factors, and underlying health conditions. This article synthesizes the key findings from recent research to provide a comprehensive overview of the causes of low WBC count.
Genetic Factors Influencing Low WBC Count
Genetic Loci and Ancestry
Genetic variations play a significant role in determining WBC counts. Research has identified specific genetic loci associated with lower WBC counts, particularly among individuals of African descent. A notable study found a strong association between a locus on chromosome 1q and WBC count, with the Duffy blood group antigen being a key marker. This genetic variant explained approximately 20% of the population variation in WBC counts among African Americans1 5. Another study confirmed that the Duffy Null polymorphism (SNP rs2814778) is predictive of WBC and neutrophil counts in African Americans, further establishing a genetic basis for lower WBC counts in this population5.
Polygenic Risk Scores
Polygenic risk scores (PRS) have also been used to predict low WBC counts. A study involving 89,559 biobank participants found that individuals with a genetic predisposition to lower WBC counts had an increased risk of leukopenia when treated with chemotherapeutic or immunosuppressant drugs. This predisposition was also associated with a higher likelihood of discontinuing azathioprine treatment due to low WBC counts2. Another study identified seven single nucleotide polymorphisms (SNPs) that were positively associated with low WBC risk, highlighting the complex genetic interactions that contribute to this condition4.
Lifestyle and Environmental Factors
Diet and Exercise
Lifestyle factors, including diet and exercise, can influence WBC counts. A study found that vitamin D intake, a plant-based diet, and regular exercise were positively related to maintaining normal WBC counts. Conversely, smoking and alcohol intake were inversely associated with WBC counts4. These findings suggest that lifestyle modifications can mitigate the risk of low WBC counts, especially in individuals with a genetic predisposition.
Chemotherapy and Immunosuppressants
Treatment with certain medications, such as chemotherapeutic agents and immunosuppressants, can lead to a decrease in WBC counts. Individuals with a genetic predisposition to lower WBC counts are particularly susceptible to this effect, which can result in the need for treatment adjustments or discontinuation2.
Health Conditions and Inflammatory Markers
Autoimmune and Inflammatory Diseases
Genetic studies have shown that many loci associated with WBC traits are also linked to autoimmune and inflammatory diseases. For instance, genes involved in myeloid and lymphoid differentiation, as well as those regulating neutrophil clearance and apoptosis, have been identified as common variants affecting WBC counts. These genetic associations suggest a shared genetic architecture between low WBC counts and inflammatory or autoimmune conditions3.
Metabolic Syndrome and Insulin Resistance
Low-grade inflammation, as indicated by high WBC counts, has been associated with metabolic syndrome and insulin resistance. A study involving Japanese men found that WBC count had a positive correlation with body mass index (BMI), blood pressure, triglycerides, glucose, and insulin levels. This suggests that metabolic syndrome components, based on insulin resistance, may cause low-grade inflammation, which in turn affects WBC counts7.
Conclusion
Low WBC counts can result from a combination of genetic predispositions, lifestyle factors, and underlying health conditions. Genetic loci, particularly those associated with the Duffy blood group antigen, play a significant role in determining WBC counts, especially among individuals of African descent. Polygenic risk scores further highlight the complex genetic interactions involved. Lifestyle factors such as diet and exercise, as well as treatments like chemotherapy and immunosuppressants, also influence WBC counts. Additionally, low-grade inflammation related to metabolic syndrome and autoimmune diseases can contribute to variations in WBC counts. Understanding these factors is crucial for managing and mitigating the risks associated with low WBC counts.
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Most relevant research papers on this topic
Admixture mapping of white cell count: genetic locus responsible for lower white blood cell count in the Health ABC and Jackson Heart studies.
A genetic locus on chromosome 1q is strongly associated with lower white blood cell count in African Americans, explaining approximately 20% of population variation in white blood cell count.
Observational Study
Highly CitedClinical consequences of a polygenic predisposition to benign lower white blood cell counts
A genetic predisposition to benign lower white blood cell counts can increase the risk of leukopenia, leukoencephalopathy, and discontinuing azathioprine treatment in clinical care.
Observational Study
PreprintLarge-Scale Exome-wide Association Analysis Identifies Loci for White Blood Cell Traits and Pleiotropy with Immune-Mediated Diseases.
16 common genetic variants are associated with white blood cell traits and autoimmune diseases, suggesting a shared genetic architecture with inflammatory and autoimmune diseases.
Meta-Analysis
Rigorous JournalAssociation between Polygenetic Risk Scores of Low Immunity and Interactions between These Scores and Moderate Fat Intake in a Large Cohort
High polygenetic risk scores are associated with a higher risk of low white blood cell count, and individuals with these scores should be advised to consume moderate fat intake and exercise regularly.
Observational Study
Very Rigorous JournalReduced Neutrophil Count in People of African Descent Is Due To a Regulatory Variant in the Duffy Antigen Receptor for Chemokines Gene
The Duffy Null polymorphism, rs2814778, is associated with reduced neutrophil count in African Americans, indicating a novel genetic phenotype for this gene.
Observational StudyHighly CitedHigh white blood cell count is associated with a worsening of insulin sensitivity and predicts the development of type 2 diabetes.
A high white blood cell count predicts worsening insulin sensitivity and the development of type 2 diabetes in Pima Indians, suggesting chronic immune activation may play a role in the development of type 2 diabetes.
Observational StudyHighly CitedAssociation of white blood cell count and clustered components of metabolic syndrome in Japanese men.
The cluster of metabolic syndrome components based on insulin resistance may cause low-grade inflammation in Japanese men aged 34-69 years.
Observational StudyHighly CitedThe United Kingdom National External Quality Assessment Scheme gating and standardization strategy for use in residual WBC counting of WBC‐reduced blood components
The daily run control (DRC) and new gating strategy enable international standardization in low-level WBC counting, reducing interlaboratory variation.
Meta‐analysis of total and differential white blood cell counts in schizophrenia
Schizophrenia is associated with increased total white blood cell count, indicating low-grade inflammation in the brain.
Meta-AnalysisVery Rigorous JournalHighly CitedFour cases of spuriously low WBC count due to in vitro leukocyte agglutination: contribution of the hematology analyzer Coulter STKS in detecting this clinically misleading artefact.
The Coulter STKS hematology analyzer can help detect in vitro leukoagglutination, potentially causing spuriously low WBC counts in blood smears.
Case Report