ABSTRACT
Database URLs: http://www.regulomedb.org/;https://www.broadinstitute.org/mpg/snap/.
Subject(s)
Coronary Artery Disease/genetics , Databases, Nucleic Acid , Genetic Loci , Linkage Disequilibrium , Polymorphism, Single Nucleotide , Signal Transduction , Animals , Coronary Artery Disease/metabolism , HumansABSTRACT
BACKGROUND: Cardiomyopathy is the leading cause of mortality in beta-thalassaemia major (BTM) patients. Brain natriuretic peptide (BNP) has been used for latent cardiac dysfunction in heart patients other than thalassaemic patients. The objective was to determine its role in subclinical detection of iron-induced cardiotoxicity in BTM patients. METHODS AND RESULTS: EDTA plasma was taken from 33 thalassaemic patients and 29 healthy controls, stored at -20 degrees C until analysis. The median (range) age of thalassaemic major children was 10 (6-21) years and mean serum ferritin levels were 3956 (1929-6979) microg/L. The BTM children had significantly (P < 0.01) higher BNP median (range) 83.94 (45.93-196.80) pg/mL as compared to controls 55.62 (32.58-99.84) pg/mL. Mitral E-wave velocities were found higher in patients rather than controls (132.12 +/- 29.40 vs. 117.70 +/- 24.81; P < 0.05). The E/Ea ratio was significantly higher in BTM patients than in the control group (16.35 +/- 6.01 vs. 19.26 +/- 4.67; P = 0.001). We found a significant positive correlation between BNP and E/Ea ratio (r = 0.53; P < 0.01). BNP at a cut-off value of 84.39 pg/mL was highly accurate in ruling out diastolic dysfunction (E/Ea < 8) with a sensitivity of 80% and a specificity of 88%. CONCLUSION: BNP has a good predictive value in detecting latent LV dysfunction in BTM patients.
Subject(s)
Natriuretic Peptide, Brain/blood , Ventricular Dysfunction, Left/blood , Ventricular Dysfunction, Left/etiology , beta-Thalassemia/complications , Adolescent , Biomarkers/blood , Case-Control Studies , Child , Echocardiography, Doppler , Female , Humans , Male , Predictive Value of Tests , ROC Curve , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/physiopathology , Young AdultABSTRACT
Viral hepatitis is common among beta-thalassemia major (BTM) children in Pakistan. Transfusional iron overload in BTM is usually monitored by serum ferritin. But its levels are falsely raised in viral hepatitis and do not reflect the true iron body burden in thalassemic patients. The objective of the study was to develop a test for monitoring iron overload in 'Hepatitis B&C' positive BTM patients by urinary iron excretion (UIE) after oral deferiprone chelation as compared to serum ferritin. We recruited 130 BTM patients from the registry of Thalassaemia centre at Rawalpindi, Pakistan. The patients were grouped into Hepatitis positive and Hepatitis negative based on ELISAtest. Serum ferritin levels were analyzed by kit on Access II. Each patient was given 75mg/kg of deferiprone at morning. Baseline UIE before deferiprone, and 4, 8 12 hours (hrs) UIE after deferiprone were analyzed on Selectra E. One hundred and thirty BTM patients aged 3 to 23 years comprising of Hepatitis positive (n=69) and Hepatitis negative (n=61) participated in the study. Hepatitis positive thalassemic patients had significantly high serum ferritin median (IQ) 4349 (2782-5927) mug/Lthan 3338 (2189-5506) mug/Lin the Hepatitis negative (p=0.001). We did not find any significant change in UIE at 4, 8, and 12 hours between two groups after Deferiprone intake (p=NS). We observed significant positive correlation between serum ferritin and 4 hours UIE in Hepatitis negative patients (r=0.57; p=0.01) but not in the Hepatitis positive patients (r=0.16; p=NS). Deferiprone challenge with measurement of 4 hours UIE is cost effective and non-invasive test rather than serum ferritin for monitoring iron overload in Hepatitis' positive BTM patients.
