PMID- 27187171
OWN - NLM
STAT- MEDLINE
DCOM- 20170707
LR  - 20190219
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 5
DP  - 2016
TI  - Impact of Genetic Polymorphism of methylenetetrahydrofolate reductase C677T on 
      Development of Hyperhomocysteinemia and Related Oxidative Changes in Egyptian 
      beta-Thalassemia Major Patients.
PG  - e0155070
LID - 10.1371/journal.pone.0155070 [doi]
LID - e0155070
AB  - BACKGROUND: beta-thalasemia major (beta-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 beta-TM has not yet been adequately defined. AIM: To 
      evaluate the genetic polymorphism of MTHFR C677T among beta-TM patients and its 
      prospective contribution to Hhcy and related oxidative changes. SUBJECTS AND 
      METHODS: 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 beta-TM patients and 66 control subjects of matched 
      age and sex. RESULTS: The prevalence of MTHFR 677TT genotype was significant 
      among beta-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 beta-TM patients with TT genotype were 
      hyperhomocystienemic (>/= 15 mumol/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 beta-TM patients with different 
      MTHFR genotypes. CONCLUSION: This study suggests that Egyptian beta-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 
      beta-TM patients.
FAU - Abd-Elmawla, Mai A
AU  - Abd-Elmawla MA
AD  - Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
FAU - Rizk, Sherine M
AU  - Rizk SM
AD  - Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
FAU - Youssry, Ilham
AU  - Youssry I
AD  - Department of Pediatric Hematology, Faculty of Medicine, Cairo University, Cairo, 
      Egypt.
FAU - Shaheen, Amira A
AU  - Shaheen AA
AD  - Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160517
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers)
RN  - 0 (Codon)
RN  - EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2))
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Alleles
MH  - Amino Acid Substitution
MH  - Biomarkers
MH  - Case-Control Studies
MH  - Child
MH  - Codon
MH  - Egypt
MH  - Female
MH  - Gene Frequency
MH  - Genotype
MH  - Humans
MH  - Hyperhomocysteinemia/diagnosis/*etiology/*metabolism
MH  - Male
MH  - Methylenetetrahydrofolate Reductase (NADPH2)/*genetics
MH  - Oxidation-Reduction
MH  - *Oxidative Stress
MH  - *Polymorphism, Genetic
MH  - Prevalence
MH  - Young Adult
MH  - beta-Thalassemia/*complications/diagnosis
PMC - PMC4871363
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/05/18 06:00
MHDA- 2017/07/08 06:00
PMCR- 2016/05/17
CRDT- 2016/05/18 06:00
PHST- 2015/09/20 00:00 [received]
PHST- 2016/04/24 00:00 [accepted]
PHST- 2016/05/18 06:00 [entrez]
PHST- 2016/05/18 06:00 [pubmed]
PHST- 2017/07/08 06:00 [medline]
PHST- 2016/05/17 00:00 [pmc-release]
AID - PONE-D-15-41495 [pii]
AID - 10.1371/journal.pone.0155070 [doi]
PST - epublish
SO  - PLoS One. 2016 May 17;11(5):e0155070. doi: 10.1371/journal.pone.0155070. 
      eCollection 2016.