title: Impact of Genetic Polymorphism of methylenetetrahydrofolate reductase C677T on Development of Hyperhomocysteinemia and Related Oxidative Changes in Egyptian β-Thalassemia Major Patients.
abstract: β-thalasemia major (β-TM) patients often suffer from various vascular complications together with increased oxidative stress. Hyperhomocysteinemia (Hhcy) has been defined as a risk factor for these complications. Genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR) C677T has been shown to cause Hhcy particularly in individuals with low B-vitamins. However, the status of homocysteine (hcy) in β-TM has not yet been adequately defined.
  
  
  
  To evaluate the genetic polymorphism of MTHFR C677T among β-TM patients and its prospective contribution to Hhcy and related oxidative changes.
  
  
  
  Genotyping for MTHFR C677T was done by PCR-RFLP technique. Plasma hcy, vitamin B12, folate, malondialdehyde (MDA), total antioxidant capacity (TAC), oxidized low density lipoprotein (oxLDL), total nitric oxide (NOx) and lipid profile were determined in 66 β-TM patients and 66 control subjects of matched age and sex.
  
  
  
  The prevalence of MTHFR 677TT genotype was significant among β-TM patients (12%) compared to (3%) controls (OR = 4.9, 95%CI:1.2-24.2,P = 0.03). A strong association between Hhcy and MTHFR TT genotype was observed (OR = 7.7, 95%CI:2.8-20.9) where all β-TM patients with TT genotype were hyperhomocystienemic (≥ 15 μmol/l) and having sub-optimal folate level than those with CT or CC genotypes. Hyperhomocystienemic patients have suffered from increased oxidative stress characterized by significant increase in plasma MDA and oxLDL, and a significant reduction of plasma TAC and total NOx. Lipid profile of those patients was severely affected indicated by reduction in HDL and HDL/LDL and elevation in atherogenic index as compared with CC genotype. Other measured parameters were not significantly different among β-TM patients with different MTHFR genotypes.
  
  
  
  This study suggests that Egyptian β-TM patients with MTHFR 677TT genotype could be at increasing risk of developing Hhcy particularly with folate deficiency. This state of Hhcy may account potentially for most oxidative changes and atherogenic vascular complications frequently reported in β-TM patients.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Mai A
authors.initials: MA
authors.lastname: Abd-Elmawla
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Sherine M
authors.initials: SM
authors.lastname: Rizk
authors.affiliation: Department of Pediatric Hematology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Ilham
authors.initials: I
authors.lastname: Youssry
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Amira A
authors.initials: AA
authors.lastname: Shaheen
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D015415:Biomarkers; D016022:Case-Control Studies; D002648:Child; D003062:Codon; D004534:Egypt; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D020138:Hyperhomocysteinemia / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D015995:Prevalence; D055815:Young Adult; D017086:beta-Thalassemia / Q000150:complications* / Q000175:diagnosis
chemical_list: D015415:Biomarkers; D003062:Codon; D042965:Methylenetetrahydrofolate Reductase (NADPH2)