Abstract

Oxidative stress has been frequently associated with the development of type 2 diabetes mellitus. Manganese superoxide dismutase (MnSOD) is one of the most important enzymes responsible for the defense against oxidative damage in the mitochondria. A polymorphism in the second exon of the MnSOD at position 16 that changes Ala into Val, induces changes in the structural conformation and mitochondrial transport of MnSOD. This polymorphism affects the scavenger activity of the enzyme and generates high reactive oxygen species which could exacerbate the development of type 2 diabetes and/or its complications. Relationship between MnSOD polymorphism and type 2 diabetes mellitus and its complications remains uncertain. This study aims to investigate the association between Ala16Val MnSOD gene polymorphism and the susceptibility to type 2 diabetes mellitus (T2DM) and its complications in the Lebanese patients. For this purpose, PCR-based direct DNA sequencing reactions were performed for genotype analysis. A significant association between Ala16Val polymorphism with T2DM as 85.7% of the Val/Val homo zygotes were diabetic compared to 37.5% for the Ala/Ala genotype (p-value less than 0.01). In addition, Val/Val genotypes showed significant high mean HbA1c levels compared to their Ala/Ala genotype indicating that these patients might suffer from a poor diabetes control. Moreover, patients with Ala16Val were at a high risk from suffering diabetic complications that included retinopathy, nephropathy and cardiovascular complications. Aim: Free radical-induced damage plays an important role in the onset of type 2 diabetes and the development of its complications. This study was undertaken to investigate the association between Ala16Val polymorphism in the MnSOD gene and the susceptibility to type 2 diabetes mellitus (T2DM) and its complications in a cohort group of the Lebanese population. Settings and design: This case-control study was conducted on 59 patients with T2DM and 40 age-matched healthy unrelated controls, recruited from different regions of Lebanon. Methods: Cases were confirmed as patients with diabetes clinically and obtained from Al Rai hospital and the Egyptian military hospital in Lebanon. Controls were healthy unrelated individuals with no history of diabetes or other genetic diseases. All subjects were genotyped for Ala16Val polymorphism (C to T) by PCR based reaction-DNA sequencing. Results: A statistically significant difference was found when genotype and allele distribution of Ala16Val (C to T) polymorphism were compared between patients with diabetes and controls [P < 0.01 by chi-squared; allelic P < 0.01, OR (95% CI) = 4.068 (1.528-10.832)]. Patients with diabetes with Ala16Val polymorphism were shown to be at higher risk for developing complications including retinopathy, nephropathy and cardiovascular complications. Patients with diabetes with Ala16Val polymorphism showed high mean HbA1c blood levels indicating that these patients may suffer from a poor diabetes control.

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