Detoxification Genomics in Children with β-Thalassemia Major: Pilot Study of Glutathione S Transferase M1, Pi & Methyltetrahydrofolate Reductase Gene Polymorphisms Combinations in β- Thalassemia Major

Abstract

Background: Children with β-thalassemia major differ regarding age at presentation, transfusion requirements and unpredictable timing, rate and severity of hemolytic crisis. The blood transfusions are associated with iron overload. Glutathione S transferase M1 (GSTM1) null mutation was reported to be associated with myocardial iron overload with low body iron. Aim of the Work: To investigate if children with β-thalassemia major have more than a detoxification enzyme defect. Materials and Methods: GSTM1, glutathione S transferase Pi (GSTPi) and methyltetrahydrofolate reductase (MTHFR) polymorphism were studied among 97 children with β-thalassemia major in a cross-sectional study. Results: The studied cohort comprised 24 (24.7%) girls and 73 (75.3%) boys. Mean hemoglobin was 5.9+/- 0.7gm%, serum iron was 145.69 +/- 58.6 mcg% and total iron binding capacity was 222.58 +/-50.66 mcg%. Of them, 68 (70.1%) demonstrated single or multiple polymorphisms (43 had GSTM1, 20 GSTPi and 32 with MTHFR polymorphisms respectively), while 29 (29.2%) did not demonstrate any polymorphism. There was no correlation between type, number of polymorphisms and clinical phenotype. Sample size and cross- sectional nature of our study did not allow genotype-phenotype correlation. Most of studied children express GSTM1, GSTPi and MTHFR gene polymorphism which was not consistent among them. Conclusion: Children with β-thalassemia major may have one or more than a detoxification/ regeneration potential enzyme gene GSTM1, GSTPi and MTHFR polymorphism. Every child with β-thalassemia major has unique genetic detoxification and regeneration abilities. The detected detoxification defects might explain the lack of predictability of occurrence of hemolytic attacks and their severity. More studies are needed to highlight impact of detoxification and regeneration genomics in β-thalassemia.

Keywords

• glutathione s transferase m1 (gstm1)
• glutathione s transferase pi (gstpi)
• methyltetrahydrofolate reductase (mthfr)
• polymorphism
• β-thalassemia major