Proline-leucine polymorphism of human glutathione peroxidase 1 in Thalassemia major

Vishal Bhargava,Richa Bhargava,Neelima Singh,Manoj Gulati

doi:10.4236/abb.2013.46091

Abstract

Thalassemia is associated with low antioxidant enzyme deficiency especially glutathione peroxidase. GPX exists in 6 isomeric forms out of which GPX1 Single Nucleotide Polymorphism is found to be associated with Thalassemia major. In our study, the determination of the allelic frequency and phenotype of a common polymorphism in Se-dependent glutathione peroxidase 1 (GPX1) was observed in Thalassemic populations. A proline/leucine variant occurs at position 197 close to the C-terminus of the protein. The genotypes encoding Pro/Pro, Pro/Leu, and Leu/ Leu are distributed according to the Hardy-Weinberg relationship. The study has been carried out in 40 Thalassemic cases and 40 control subjects. No significant association between allele frequency and risk to get fatal was evident. Erythrocyte GPX activity was determined and no significant differences were obtained between the genotypes. It can be concluded that the Pro/Leu genetic variation does not appear to compromise the defense against oxidative stress in red blood cells or to be associated with significant pathology.

Highlights

Human glutathione peroxidase 1 is an abundant and widely distributed seleno-protein [1]
GPX exists in 6 isomeric forms out of which glutathione peroxidase 1 (GPX1) Single Nucleotide Polymorphism is found to be associated with Thalassemia major
We observed allelic frequency in 80 Thalassemic cases/ controls with known erythrocyte GPX activity

Summary

Introduction

Human glutathione peroxidase 1 is an abundant and widely distributed seleno-protein [1]. Mouse knock-out models have revealed that loss of the enzyme confers no obvious phenotype but the animals become more sensitive to oxidative stress [2]. Various antioxidant enzyme activities have been determined in blood. Considerable variation in antioxidant capacity does occur in humans, the variation does not account for disease susceptibility in the majority of cases [6,7,8,9]. It must either be concluded that oxidative stress is of limited importance or that current measurements of antioxidant capacity is a blunt instrument. As intra individual variation in antioxidant capacity is well documented and influenced by nutriational status [1012], other measurements of antioxidant capacity involving determination of genetic profile are highly desirable

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