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Title: Glutathione S-transferase M1 and T1 (rs4025935 and rs71748309) null genotypes are associated with increased susceptibility to coronary artery disease in Indian populations
Author(s): R. Mir , M.A. Bhat , J. Javaid , N. Shah , P. Kumar , E. Sharma , C. Jhu , S. Basak , D. Amle , P.C. Ray , A. Saxena , S. Banu
Journal: Acta Cardiologica
Volume: 71    Issue: 6   Date: 2016   
Pages: 678-684
DOI: 10.2143/AC.71.6.3178186

Abstract :
Background: Various other biochemical and genetic factors apart from conventional risk factors are known to play an important role in the pathogenesis of coronary artery disease. Polymorphism in the glutathione S-transferases gene leads to alteration in glutathione S-transferase levels which play an important role in detoxification of free radicals particularly those present in cigarette smoke.
Methods: One hundred angiographically diagnosed subjects and 100 normal controls were recruited. Detailed history and clinical examination of blood samples were collected and assessed for various biochemical parameters. GSTM1 and GSTT1 genotyping for GST gene was done by using multiplex polymerase chain reaction (PCR).
Results: The frequency of the GSTM1null genotype was found to be significantly higher in cases in the total population (P < 0.0003), in smokers (P = 0.018) and in subjects with hypertension (P = 0.04). Though distribution of the GSTT1null genotype was not found to be significantly different in cases and controls, its concomitant presence with the GSTM1null genotype was found to increase the risk of CAD in all subjects (OR = 2.28) and in smokers (P = 0.03), and to pose an additional risk in hypertensive (P = 0.01) and diabetic (P < 0.001) subjects. The most likely explanation for these findings may be that polymorphisms in the GST gene lead possibly to alteration in GST levels or activity which may further lead to variable detoxification of various toxins, mostly epoxides, including those present in cigarette smoke.
Conclusion: We conclude that GSTM1null genotype increases the risk of CAD in all subjects including smokers. Concomitant presence of GSTT1null and GSTM1null genotype was found to further increase the risk in all subjects: smokers, diabetic and hypertensive patients.

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