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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 β-globin gene ( HBB) in 154 patients with SCD [105 haemoglobin (Hb)SS, 46 HbSC and three HbS/ β0 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. [ABSTRACT FROM AUTHOR]

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 α-thalassaemia could explain some of the inconsistent effects. The UGT1A1 [TA]n and HMOX1 [GT]n promoter polymorphisms and α globin genotypes were determined in 263 SCD patients (199 HbSS, 5 HbS/ β0, 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 α-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. [ABSTRACT FROM AUTHOR]

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.