Glutathione S-Transferase (GSTT1 rs17856199) and Nitric Oxide Synthase (NOS2 rs2297518) Genotype Combination as Potential Oxidative Stress-Related Molecular Markers for Type 2 Diabetes Mellitus

Abstract

Amani MT Gusti,1,2 Safaa Y Qusti,1 Suhad M Bahijri,3,4 Eman A Toraih,5,6 Samia Bokhari,7 Sami M Attallah,8,9 Abdulwahab Alzahrani,10 Wafaa MA Alshehri,11 Hawazin Alotaibi,12 Manal S Fawzy13,14 1Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Medical Laboratory, Biochemistry, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia; 3Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 4Saudi Diabetes Research Group, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, Saudi Arabia; 5Department of Surgery, Tulane University, School of Medicine, New Orleans, LA, USA; 6Department of Histology and Cell Biology (Genetics Unit), Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 7Department of Endocrinology and Diabetes, King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia; 8Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 9Department of Clinical Pathology, King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia; 10Department of Molecular Biology, King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia; 11Department of Chemistry, Faculty of Science, University of Bisha, Al Namas, Saudi Arabia; 12Ministry of Health, Jeddah, Saudi Arabia; 13Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 14Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar, Kingdom of Saudi ArabiaCorrespondence: Manal S FawzyDepartment of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, 41522, EgyptTel + 20 1008584720Fax + 20 64 3216496Email [email protected]: Deregulation 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.Purpose: We 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 Methods: A 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.Results: After 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.Conclusion: The oxidative stress-related molecular markers, GSTT1 rs17856199 and NOS2 rs2297518 variants were significantly associated with T2DM risk and phenotype in the study population.Keywords: single nucleotide polymorphism, GSTT1, NOS2, oxidative stress, T2DM

Keywords

• single nucleotide polymorphism
• gstt1
• nos2
• oxidative stress
• t2dm