Document Details
|
Document Type |
: |
Thesis |
|
Document Title |
: |
Association of Antioxidant gene polymorphisms and Type 2 Diabetes Mellitus in Saudi Population علاقة تعدد الأشكال الجينية المضادة للأكسدة ومرض السكري من النوع الثاني في المجتمع السعودي |
|
Subject |
: |
Faculty of Science |
|
Document Language |
: |
Arabic |
|
Abstract |
: |
Deregulation of the antioxidant enzymes was implicated in pathogenesis and complications of type 2 diabetes mellitus (T2DM). This study 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. The current study was conducted on 384 Saudi participants. Of the diabetic group (T2DM), males and females were equally reported in the study population; 95 females (53.7%) versus 82 male subjects (46.3%). Different genotypes of the genes mentioned above were characterized using TaqMan OpenArray Genotyping assays on QauntStudio 12K Flex Real-Time PCR System. Among the studied 13 variants, the NOS2 rs2297518*A allele was more frequent among 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). After age- and sex-adjustment, 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. Having combined nNOS rs2297518*A and GSTT1 rs17856199*A or *C genotypes were more likely to develop T2DM. Different associations with sex, BMI, hyperglycemia, and/or hyperlipidemia were evident. According to body mass index, 154 (40.1%) of the participants were obese. Among the studied variants, seven SNPs were significantly more prevalent in obese cohorts: (1) GSTM1 rs1056806*C/T heterozygosity (21% vs 12%, p=0.039); (2) SOD1 rs2234694*A allele (100% vs. 97%, p=0.048); (3) SOD2 rs4880*G allele (52% vs. 43%, p=0.038); (4) SOD3 rs2536512*A allele (56% vs. 51%, p<0.001); (5) GPX1 rs1800668*A allele (25% vs. 19%, p=0.041); (6) GPX3 rs151028993*T (T allele: 99% vs. 96%, p=0.016; T/T genotype: 97% vs. 93%, p<0.001); and (7) NOS3 rs1799983*G allele (83% vs. 75%, p=0.029). Inheritance association models revealed that four SNPs showed a higher obesity risk; under heterozygote comparison (C/T vs. C/C: OR=2.02, 95%CI =1.15-3.55, p=0.015) and dominant (C/T-T/T vs. C/C: OR=1.92, 95%CI=1.11-3.31, p=0.019) models for GSTM1 rs1056806 (C/T), under homozygote comparison model (G/G vs A/A: OR=1.97, 95%CI=1.0-3.86, p=0.045) for SOD2 rs4880 (A/G), and under homozygote comparison (G/G vs. A/A: OR=2.65, 95%CI=1.11-6.32, p=0.048) and recessive (G/G vs. A/A-A/G: OR=2.63, 95%CI=1.12-6.18, p=0.024) models for GPX1 rs1800668 (A/G). In contrast, SOD3 rs2536512 were less likely to be obese under heterozygote comparison (A/G vs A/A: OR=0.47, 95%CI=0.26-0.83, p=0.033) and dominant (A/G-G/G vs. A/A: OR=0.53, 95%CI=0.31-0.91, p=0.021) models. In conclusion, our results suggest that oxidative stress-related molecular markers, GSTT1 rs17856199, and NOS2 rs2297518 variants, have a significant association with T2DM risk and phenotype, and the oxidative stress-related genetic determinants could have a significant association with obesity risk in the study population. |
|
Supervisor |
: |
Prof. Dr Safaa Yousef Mohammad Qusti |
|
Thesis Type |
: |
Doctorate Thesis |
|
Publishing Year |
: |
1443 AH
2022 AD |
|
Added Date |
: |
Sunday, January 8, 2023 |
|
Researchers
| أماني محمد قستي | Gusti, Amani Mohammed | Researcher | Doctorate | |
|
Back To Researches Page
|