Association of the Endothelial Nitric Oxide Synthase ( <scp>eNOS</scp> ) <scp>G894T</scp> Gene Polymorphism With Type 2 Diabetes Mellitus in a Tunisian Population

Abstract

ABSTRACT Background Type 2 Diabetes Mellitus (T2D) is a multifactorial metabolic disorder with a significant genetic component. Endothelial dysfunction, characterised by reduced nitric oxide (NO) bioavailability, is a key pathological feature. The endothelial nitric oxide synthase (eNOS) gene ( NOS3 ) contains several polymorphisms, with the G894T (Glu298Asp) variant being a prominent candidate for influencing disease susceptibility. Objective This study aimed to investigate the association between the eNOS G894T polymorphism and the risk of T2D in a sample of the Tunisian population. Methods We conducted a case–control study including 100 T2D patients and 100 non‐diabetic controls recruited from the Military Hospital of Tunis. Anthropometric, clinical and biochemical parameters, including lipid profiles and high‐sensitivity C‐reactive protein (CRPus), were measured. Genotyping of the eNOS G894T polymorphism was performed using the Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR‐RFLP) method with the Ban II restriction enzyme. Results T2D patients exhibited significantly higher levels of triglycerides (1.99 ± 1.27 vs. 1.45 ± 0.65 mmol/L, p = 0.002) and CRPus (2.73 ± 2.47 vs. 1.63 ± 1.42 mg/L, p = 0.003) compared to controls. The frequency of the mutated T allele was significantly higher in the T2D group than in the control group (27.53% vs. 11.27%, p &lt; 10 −3 ). Consequently, the heterozygous GT genotype was more prevalent among patients (55.07% vs. 19.72%, p &lt; 10 −3 ). The presence of the T allele was associated with a significantly increased risk of T2D (Odds Ratio [OR] = 4.495, 95% Confidence Interval [CI] = 2.14–9.44). Conclusion The eNOS G894T polymorphism is a significant genetic risk factor for type 2 diabetes in the studied Tunisian population. The T allele appears to confer susceptibility, likely through mechanisms involving impaired eNOS function, reduced NO production and subsequent endothelial dysfunction.

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Affiliated Institutions

• Habib hospital Thameur TN
• University of Monastir TN
• Military Hospital of Tunis TN

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