Aim: We aimed to evaluate the influence of the Gly972 Arg and Ala513Pro variants of the insulin receptor substrate1 gene (IRS1) and the Gly1057 Asp variant in IRS on type 2 diabetes mellitus (T2DM) in Arab and Berber men and women from Djerba Island, Tunisia. Methods: Genotypes, allelic and genotypic frequencies were studied. The amplified products were analyzed by Restriction Fragment Length Polymorphism (RFLP) methods by comparing T2DM with healthy controls from the same ethnicity.
Type 2 diabetes mellitus (T2DM) is characterized by three major metabolic abnormalities: impaired insulin-stimulated glucose uptake in muscle and adipose tissues, alterations in glucose-stimulated insulin secretion, and increased hepatic glucose production. Both genetic and environmental factors contribute to its development. The insulin gene (INS), insulin receptor gene (INSR), and insulin receptor substrate 1 gene (IRS1), identified by polymerase chain reaction and digestion with selected restriction enzymes PstI, NsiI, and BstnI, have been proposed as T2DM candidate genes. To determine the contribution of genetic and environmental factors on the occurrence of T2DM, we examined the frequency of T2DM among two ethnically diverse populations, Arabs and Berbers, who have shared the same environment, the island of Djerba, for thousands of years. Both populations have a high prevalence of obesity,T2DM, and a high consanguinity rate. A total of 162 T2DM men and women were matched to 110 healthy male and female controls. Results showed that the NsiI polymorphism in INSR and BstnI polymorphism of IRS1 were significantly associated with T2DM only among the Berber group. The PstI polymorphism in INS, was not associated with T2DM in either group. Sedentary lifestyles, lower physical activity, and lower educational levels were associated with T2DM among the Berber group. These findings suggest that the insulin receptor gene and lifestyle factors in combination may contribute to the occurrence of T2DM in the Berber portion of this island population.
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