Abstract

BackgroundDeregulation of the antioxidant enzymes was implicated in pathogenesis and complications of type 2 diabetes mellitus (T2DM). The data relate the genetic variants of these enzymes to T2DM are inconsistent among various populations.PurposeWe aimed to explore the association of 13 genetic variants of “superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and nitric oxide synthase (NOS)” with T2DM susceptibility and the available clinical laboratory data.Subjects and MethodsA total of 384 individuals were enrolled in this work. Different genotypes of the genes mentioned above were characterized using TaqMan OpenArray Genotyping assays on a Real-Time polymerase chain reaction system.ResultsAfter age- and sex-adjustment, among the studied 13 variants, GSTT1 rs17856199 was associated with T2DM under homozygote (OR=3.42; 95% CI:1.04–11.2, p=0.031), and recessive (OR=3.57; 95% CI: 1.11–11.4, p=0.029) comparison models. The NOS2 rs2297518*A allele was more frequent among the T2DM cohort (58.1% vs 35.4%, p<0.001) and showed a dose-response effect; being heterozygote was associated with higher odds for developing DM (OR=4.06, 95% CI=2.13–7.73, p<0.001), whereas being AA homozygote had double the risk (OR=9.06, 95% CI=3.41–24.1, p<0.001). Combined NOS2 rs2297518*A and either GSTT1 rs17856199*A or *C genotype carriers were more likely to develop T2DM. Different associations with sex, BMI, hyperglycemia, and/or hyperlipidemia were evident. The principal component analysis revealed NOS2 rs2297518*G, old age, dyslipidemia, high systolic blood pressure, and elevated HbA1c were the main classifiers of T2DM patients.ConclusionThe oxidative stress-related molecular markers, GSTT1 rs17856199 and NOS2 rs2297518 variants were significantly associated with T2DM risk and phenotype in the study population.

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