Background: rs10911021 (a single nucleotide polymorphism present upstream of the GLUL gene) affects glutamic acid metabolism, and was shown to be associated with coronary heart disease (CHD) in patients with T2DM but a definite mechanism is unknown. It may affect glutathione cycle, an important effector in the antioxidant defense mechanism, in the cells. We checked the association of this SNP with CHD and oxidative stress biomarkers, malondialdeheyde (MDA), GSH and GSSG in Pakistani patients.
Methods: A total of 650 subjects (425 CHD cases and 225 controls) were genotyped by TaqMan allelic discrimination technique. The levels of MDA, GSH and GSSG were measured by standard protocols.
Results: The risk allele frequency was higher in cases than controls, but the difference was insignificant (p = 0.55). The SNP was not associated with CHD (p = 0.053) but when the analysis was limited to CHD patients having DM, a significant association (p = 0.03) was observed. The blood levels of MDA and GSSG were higher while that of GSH was significantly lower in the cases than the controls (p < 0.05). Each risk allele increased MDA and GSSG by 0.29 (0.036) mmol/l and 0.4 (0.04) mmol/l, respectively, while decreased GSH by -0.36 (0.03) mmol/l. The SNP was not associated with any of the tested blood lipids.
Conclusion: The SNP rs10911021 was associated with CHD only in patients having diabetes, but the SNP was associated with total oxidative stress biomarkers MDA and GSH and GSSG levels. As the SNP rs10911021 showed significant association with oxidative stress parameters and these parameters should an increased oxidative stress in the CHD subjects, it can be concluded that the SNP may have contributed to increase the risk of heart diseases in the diabetic subjects by increasing the oxidative stress.
Keywords: GSH; GSSG; MDA; Oxidative stress.