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.

P53 Mutation at Codon 249 is Uncommon in Neonatal Kotb Disease Biliary Atresia

“…And how long will it take to eliminate it after ingestion in humans ( 23)? Yet, we know that we have individualized detoxification genomics (24), and we know that at times we get exposed to more than a mycotoxin (25) in our meals, hence the response to aflatoxin load is not typical as a lot of factors and interaction governs the individual response to aflatoxin (26). All our studied cohort and their mothers had elevated aflatoxin B1 levels, hence, they all suffered from Kotb disease BA variant.…”

Association of glutathione S-transferases (GSTT1, GSTM1 and GSTP1) genes polymorphisms with nonalcoholic fatty liver disease susceptibility: A PRISMA-compliant systematic review and meta-analysis

“…Consequently, it proved that detoxification defects that confered host susceptibility, but were not the sole determinant factor of disease pathogenesis, elinical picture, march or outcome. [54] Up to now, this is the first synthetical study on the relationship between GSTs polymorphisms and NAFLD vulnerability. There were several strengths in this study.…”

“…Consequently, it proved that detoxification defects that confered host susceptibility, but were not the sole determinant factor of disease pathogenesis, elinical picture, march or outcome. [ 54 ]…”