Journal
HUMAN GENE
Volume 35, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.humgen.2022.201138
Keywords
GSTM1; T1 polymorphisms; MTHFR C677T SNP; Systemic arterial hypertension; Type 2 diabetes mellitus; Genetic susceptibility
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This genetic association study found that both GSTM1 and GSTT1 null and mutant genotypes (677TT) conferred risk to hypertension susceptibility in hypertensive diabetic patients. The combined genotypes (MTHFR:GSTT1:GSTM1) revealed a significant association, suggesting an oxidative hypothesis for the development of hypertension in diabetic patients. Imbalance in antioxidant enzymes and homocysteine metabolism may contribute to the establishment of oxidative stress in these patients.
This genetic association study included 150 hypertensive diabetic patients and 150 normotensives non-diabetic subjects. Glutathione S-transferases M1 and T1 (GSTM1/GSTT1) deletion polymorphisms and methylenetetrahydrofolate reductase (MTHFR) C677T SNP (rs1801133) genotyping were performed by SYBR Green multiplex realtime and RFLP-PCR, respectively. Both GSTM1 and GSTT1 null (OR = 4.52, p = 0.04, and OR = 4.27, p = 0.01) and mutant (677TT) genotypes (OR = 2.95, p = 0.02) conferred risk to hypertension susceptibility. The combined genotypes (MTHFR:GSTT1:GSTM1) revealed a significant association: W/-/+, W/+/-, H/-/-, H/-/+, M/+/-, and M/+/+. These findings suggesting a probable oxidative hypothesis for hypertensive diabetic patients from the interaction of the detoxification mechanism and the homocysteine metabolism. The imbalance in antioxidant enzymes contributes to the establishment of oxidative stress in conjunction with hyperhomocysteinemia and reactive oxygen species production. We concluded that these findings suggest that both polymorphisms may contribute to hypertension susceptibility in diabetic patients.
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