Role of Glutathione S Transferase Polymorphism in the Pathogenesis of Cardiovascular Diseases: A Case Control Study
Role of Glutathione S Transferase Polymorphism in the Pathogenesis of Cardiovascular Diseases: A Case Control Study
Muhammad Akram1*, Muhammad Imtiaz Shafiq2, Amber Malik3, Farmanullah Khan4, Munir Ahmad Bhinder5 and Muhammad Sajjad6
ABSTRACT
Cardiovascular diseases (CVDs) are major health problems all over the world. Oxidative stress contributes an important pathological role in the development of CVDs. To counter this oxidative stress, the most important natural antioxidant defense mechanisms include endogenous glutathione concentration, superoxide dismutase, catalase, and glutathione S-transferase (GST). GST neutralizes reactive oxygen species to regulate physical homeostasis in the body. The target of this study was to evaluate the molecular role of GST genotypic polymorphism involved in the development of CVD. For this case-control study, a total of 504 participants including 261 CVD patients and 243 healthy individuals were enrolled after taking informed consent. The analysis of the three allelic variants GSTM1, GSTT1, and GSTP1 was carried out through PCR-based amplification. Amplification of GSTM1 and GSTT1 was performed using the specific primers designed by Primer-3 software. GSTT1 and GSTMI genotypes were determined by comparing the sizes of amplified PCR product of genotypes with β Globulin gene, used as internal standard and 100-bp DNA ladder. GSTP1 genotype was determined using the PCR-restriction fragment length polymorphism. Analysis of data was carried out using SPSS software Version 22.0. Statistical significance of p< 0.05 was considered as valuable results. Results demonstrated that Null and GSTP1b(105) genotypes were more frequent in CVD patients than controls (23.0 vs 8.6 and 69.0 vs 44.4) with strong statistical association of Null=OR: 0.317, CI: 0.126-0.797 and GSTP1b(105) OR: 0.360, CI: 0.192 – 0.677 respectively. GSTM1 and GSTT1 were less frequent in CVD patients (46.0% vs 74.1% and 49.4% vs 74.1%) with significant statistical association of GSTM1= OR: 3.367, CI: 1.75-6.44 vs GSTT1=OR: 2.292, CI: 1.52-5.60 respectively. These findings concluded that Null and GSTP1b(105) genotypes have a significant association with CVD in the Pakistani population.
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