Asunto(s)
Anemia de Células Falciformes/complicaciones , Proteína Morfogenética Ósea 6/genética , Osteonecrosis/etiología , Adolescente , Adulto , Anexina A2/genética , Femenino , Necrosis de la Cabeza Femoral , Predisposición Genética a la Enfermedad , Glucuronidasa/genética , Humanos , Proteínas Klotho , Masculino , Persona de Mediana Edad , Osteonecrosis/genética , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
Hydroxyurea reduces the frequency of acute pain in sickle cell disease (SCD). We sought to determine if hydroxyurea therapy affects cell free DNA (cfDNA) levels in SCD. cfDNA levels fell in all 10 patients studied; before hydroxyurea, mean was 1,879 (95% CI 1,104-3,199) GE/mL; after hydroxyurea, mean was 780 (95% CI, 634-959) GE/mL (P = 0.002). Mean cfDNA level in the 10 HbSS adults prior to starting hydroxyurea was also significantly higher than that in 115 HbSS case controls who had never taken hydroxyurea (1,879 vs 975 GE/mL, P = 0.02). cfDNA levels may be useful in monitoring response to hydroxyurea therapy in SCD.
Asunto(s)
Anemia de Células Falciformes/tratamiento farmacológico , ADN/sangre , Hidroxiurea/uso terapéutico , Adolescente , Adulto , Anciano , Anemia de Células Falciformes/sangre , Biomarcadores , Muerte Celular/efectos de los fármacos , Femenino , Humanos , Hidroxiurea/farmacología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sesgo de SelecciónRESUMEN
Free circulating DNA is present in the plasma of healthy subjects, and is elevated in conditions characterized by increased cell death, such as cancer and physical trauma. Analysis of circulating DNA in plasma could provide a useful biomarker in sickle cell disease (SCD) in view of the increased cell turnover through chronic ongoing haemolysis, recurrent vaso-occlusion and inflammation. Plasma DNA was determined by real-time quantitative polymerase chain reaction (PCR) amplification of the beta-globin gene (HBB) in 154 patients with SCD [105 haemoglobin (Hb)SS, 46 HbSC and three HbS/beta(0) thalassaemia] and 53 ethnically matched controls. Blood samples were obtained from all patients in steady state; 21 of the 154 patients were also sampled during admission to hospital for acute pain. Median concentration of circulating plasma DNA in acute pain was more than 10-fold that in steady state and in controls - 10070 vs. 841 and 10070 vs. 933 genome equivalents/ml respectively (P < 0.0001, in both cases). During steady state, patients had plasma DNA levels similar to controls. Plasma DNA levels in SCD correlated with C-reactive protein levels (P < 0.005) and total white cell counts (P < 0.05) in steady state. The study shows that plasma DNA concentration may have potential as a biomarker in sickle cell patients.
Asunto(s)
Anemia de Células Falciformes/sangre , ADN/sangre , Enfermedad Aguda , Adolescente , Adulto , Anemia de Células Falciformes/inmunología , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Femenino , Humanos , Recuento de Leucocitos , Modelos Lineales , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Common sequence variants situated between the HBS1L and MYB genes on chromosome 6q23.3 (HMIP) influence the proportion of F cells (erythrocytes that carry measurable amounts of fetal hemoglobin). Since the physiological processes underlying the F-cell variability are thought to be linked to kinetics of erythrocyte maturation and differentiation, we have investigated the influence of the HMIP locus on other hematologic parameters. Here we show a significant impact of HMIP variability on several types of peripheral blood cells: erythrocyte, platelet, and monocyte counts as well as erythrocyte volume and hemoglobin content in healthy individuals of European ancestry. These results support the notion that changes of F-cell abundance can be an indicator of more general shifts in hematopoietic patterns in humans.
Asunto(s)
Plaquetas/citología , Cromosomas Humanos Par 6 , ADN Intergénico/fisiología , Eritrocitos/citología , Genes myb , Monocitos/citología , Factor 1 de Elongación Peptídica/genética , Recuento de Células Sanguíneas , Cromosomas Humanos Par 6/química , Femenino , Humanos , Masculino , Polimorfismo de Nucleótido SimpleRESUMEN
Serum bilirubin levels and predisposition to gallstones in sickle cell disease (SCD) are influenced by genetic variation in the hepatic uridine diphosphate (UDP)-glucuronosyltransferase (UGT1A1) gene, but the association is not consistent. This study investigated whether variation in the gene encoding haem oxygenase (HMOX1), a rate-limiting enzyme upstream of UGT1A in the haem catabolic pathway, and alpha-thalassaemia could explain some of the inconsistent effects. The UGT1A1 [TA](n) and HMOX1 [GT](n) promoter polymorphisms and alpha globin genotypes were determined in 263 SCD patients (199 HbSS, 5 HbS/beta(0), 59 HbSC). Detection of gallstones was based on ultrasound of the liver/biliary tree. Regression analysis showed that serum bilirubin levels and the incidence of gallstones were strongly associated with the number of UGT1A1 [TA] repeats in all subjects (P < 0.0001 and P < 0.01, respectively). While HMOX1 genotype had no effect, co-inheritance of alpha-thalassaemia reduced serum bilirubin levels in all SCD patients independently of the number of UGT1A1 [TA] repeats. Each additional [TA] repeat is associated with an increase in mean serum bilirubin levels of 21% and cholelithiasis risk of 87% in SCD.