Abstract
Beta-thalassemia major (β-TM) in children is associated with an increase in the risk of premature cardiovascular complications caused by accelerated atherosclerosis which significantly contributes to morbidity and mortality. The molecular mechanisms underlying β-TM associated atherosclerosis and its relation to biochemical risk factors still remain obscure. We aimed to investigate the association between SIRT1 single nucleotide polymorphism (SNP), lipid profile, ferritin, malondialdehyde (MDA), 8-hydroxydeoxy guanosine (8-OHdG) and total antioxidant capacity (TAC) in relation to carotid intima media thickness (CIMT) trying to explain some mechanisms of cardiovascular complication in beta-Thalassemia major (β-TM) children. This study was carried out on 100 Egyptian children with β-TM (Group II) subdivided equally according to CIMT into Group IIa, with CIMT<0.5 mm and Group IIb with CIMT ≥ 0.5 mm, in addition to 50 healthy children as controls (Group I). All groups were subjected to measurement of plasma Ferritin, lipid profile, MDA and TAC colorimetrically. 8-OHdG levels were estimated by enzyme-linked immunosorbent assay (ELISA) in addition genotyping pattern for the SIRT1 (rs7069102) SNP was evaluated using PCR-CTPP technique. Values for AIP, ferritin, MDA and 8-OHdG levels, were significantly higher in β-TM groups compared to control with higher levels in patients with CIMT more than 0.5 mm but values of TAC and (HDL-C) showed significant decrease. CIMT was significantly correlated with age, atherogenic index of plasma (AIP), ferritin, MDA and 8-OHdG, HDL-C and TAC. There was significant difference in C allele distribution of SIRT1 rs7096102 was 57% in control subjects, 29% in Group IIa and 23% in Group IIb. However, the allele G distribution was 43% in control subjects, 71% in Group IIa and 77% Group IIb. Significant association of SIRT1 (rs7069102) polymorphism with dyslipidemia, ferritin and oxidative stress may conduct atherosclerotic potential in β-TM by affecting the severity of CIMT. Key words: Beta-thalassemia major, carotid intima media thickness.
Highlights
Beta-thalassemia (β-TM) represents the commonest cause of hemolytic anemia in Egypt with carrier rate ranges from 9-10% (Li, 2017)
It was performed on a number of predictors including plasma levels of ferritin, TAG, high density lipoprotein-cholesterol (HDL-C), atherogenic index of plasma (AIP), MDA, 8-OHdG and total antioxidant capacity (TAC) as independent variables, and carotid intima media thickness (CIMT) as the dependent variable
It was found that ferritin followed by 8-OHdG levels were the most important predictors of CIMT
Summary
Beta-thalassemia (β-TM) represents the commonest cause of hemolytic anemia in Egypt with carrier rate ranges from 9-10% (Li, 2017). The mechanisms underlying the accelerated atherosclerosis in β-TM are not clear because the traditional risk factors fail to account fully for the excess of cardiovascular events in βTM patients. It has been suggested that patients with β-TM possess additional risks in addition to the traditional risk factors for the development of accelerated atherosclerosis (Tantiworawit et al, 2016). Beside the traditional diagnostic methods such as angiography and stress-testing, measurement of the intima-media (IMT) thickness of the large arteries, especially the carotids, is a non-invasive predictor of early arterial wall alteration, which identifies and quantifies early structural vascular abnormalities and is currently considered as a marker of premature atherosclerosis and is predictive of future cardiovascular events (Plasencia and García, 2017)
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