MTHFR C677T Polymorphism, Plasma Homocysteine, and PDGF-AA Levels and Transcranial Doppler Velocity in Children With Sickle Cell Disease.

OBJECTIVE: To evaluate the effect of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on plasma homocysteine (tHcy) and platelet-derived growth factor (PDGF-AA) levels in children with sickle cell disease (SCD), and ascertain their role in predicting high transcranial doppler velocity (TCD). METHODS: We estimated MTHFRC677T gene poly-morphism, plasma tHyc and PDGF-AA in 44 SCD patients and 44 healthy children. RESULTS: The prevalence of mutant homozygous MTHFR (C677TT) in SCD was 13.6%. Significantly higher plasma tHcy was observed in mutant homozygous MTHFRC677TT patients. Significantly higher plasma tHcy and PDGF-AA levels were observed in SCD patients than in controls. Median (IQR) PDGF-AA levels were significantly higher in conditional and high-risk TCD patients as compared to low-riskTCD patients [325 (93.1-368) and 368 (111-480) vs 111 (56-201) pg/mL, respectively; P<0.001]. Mean (SD) tHcy levels were significantly higher in high-risk TCD children than low-risk TCD children (12.9 (2.7) vs 9.9 (2.5) µmol/L; P=0.006). The receiver operating characteristic revealed that the area under the curve (AUC) of PDGF-AA for high TCD velocity was 0.934 (95% CI 0.845-1.00; P<0.001) and tHcy had an AUC of 0.675 (95% CI 0.517-0.833; P=0.04). CONCLUSION: PDGF-AA and tHcy levels could be used as predictive markers for stroke in SCD children. MTHFR Polymorphism contributes to elevated tHcy levels.

Endothelial nitric oxide synthase gene polymorphism (786T/C) in childhood acute lymphoblastic leukemia survivors.

OBJECTIVES: To detect eNOS gene polymorphism and its relation to cardiovascular complications in pediatric acute lymphoblastic leukemia (ALL) survivors. METHODS: CBC, renal and liver function tests, lipid profile, Carotid artery Intima Media Thickness (CIMT), and Brachial artery Intima Media Thickness (BIMT). eNOS gene polymorphism was done in 40 childhood ALL survivors and 40 controls. RESULTS: There was no significant difference between survivors and control groups regarding 786 T/C polymorphism. There was a significant increase in serum cholesterol, TGs, LDL, VLDL, and HbA1c in the TC and CC group more than in the TT group, while there was a significant decrease in serum HDL in the TC and CC group more than in the TT group. There was no significant difference as regards echocardiography findings between different polymorphisms of 786 T/C, but there was a significant difference between 786 T/C groups with regard to the carotid and brachial arteries intima media thickness (IMT) measurements being significantly higher in the TC and CC group more than in the TT group. CONCLUSION: Carotid and brachial arteries intima media thickness measurements were higher in the survivors when compared to healthy controls. eNOS gene polymorphism may play a role in modifying or developing CVD in pediatric ALL survivors.