Glutamate cysteine ligase (GCL) is an enzyme that catalyzes the synthesis of glutathione (GSH). Glutathione is considered as significant antioxidant and have crucial role in the regulation of the immune system and and restrains the development of Mycobacterium tuberculosis1,2. Glutathione (γ-glutamylcysteine glycine) is a tripeptide; containing three amino acids: glutamate, cysteine and glycine. Glutathione formation involves two phases and each step is catalyzed through different enzyme. In first step, the synthesis of dipeptide γ-glutamyl cysteine involves a catalyst named as glutamate-cysteine ligase (GCL). While in the 2nd phase, glutathione formation from γ-glutamyl cysteine and glycine is aided by catalyst; “glutathione synthetase (GSS)”3 GCL has further 2 components; the catalytic subunits (GCLC) and the modulator subunits (GCLM).
Sometimes, due to certain factors, polymorphism (the existence of more than one form of phenotype in the same population of a species) occurs. Generally, genetic variation leads towards different morphisms in a population existing in diverse environments.4It is reported that genetic polymorphisms in GCLC and GCLM genes lead towards low levels of abridged glutathione (GSH) in vitro which ultimately cause various ailments5. For instance, this phenomenon is interlinked with impaired lung’s functionality6. Moreover, TB patients having alleged GCL gene polymorphism are more vulnerable to oxidative stress, which magnify the disorder.
Accordingly, Ari Yuniastuti, R. Susanti and Dewi Mustikaningtyas performed an experiment to evaluate the GCLC polymorphism in patients suffering with pulmonary tuberculosis (TB). Scientists collected the blood samples of 225 TB patients from the central public health in Semarang city. Afterwards, team conducted the genetic test through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The isolation of DNA was carried out by utilizing DNA extraction kit. Moreover, the magnification of GCLC fragment was conducted by a master mix from Thermo Scientific and data was examined descriptively. Later, for statistical analysis, Chi-square test was used.
Ari Yuniastuti and team noted the occurrence of polymorphism-129C/T in the 5’-flanking region of GCLC genes with frequency of C/C and C/T genotype; 63.6 and 36.4%, correspondingly. The C/T gene in the GCLC -129C region is a T gene promoter. Major difference was observed between C/C and C/T frequencies with significance value of p = 0.000 (p<0.05). Accordingly, scientists concluded that the frequency of C/T polymorphism genotype of GCLC gene in TB is 36.4%. This investigation can assist in gaining authentic information regarding addition of antioxidants (Vit C, Vit E, etc.) to uphold their levels in the body during TB treatment which is beneficial to avoid the oxidative stress.
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17 November, 2019