Genetic Variability Within ADA Gene and Susceptibility to Type 2 Diabetes in Obese Subjects

Abstract

The complex relationship between adenosine, obesity and Type 2 Diabetes (T2D) prompted us to investigate a possible role of genetic variability within adenosine deaminase (ADA) gene in the susceptibility to T2D in obese subjects.  With enzymatic activity ADA contributes to the regulation of adenosine concentration in body fluids and as ecto- enzyme modulates signaling events involving adenosine receptors on cell surface.Three polymorphic sites within the ADA gene, ADA1 (exon 1), ADA2 (intron 2) and ADA6 (exon6) were examined in 299 subjects from the White population of Rome admitted to the Hospital for cardiovascular diseases. Each site shows two alleles: the alleles with higher frequency are ADA1*1, ADA2*1 and ADA6*2.Informed consent was obtained by the patients to participate to the study that was approved by the Council of Department.For the three sites examined the relative risk of T2D in obese subjects (vs non obese) is higher in carriers of the homozygous genotype for the allele with higher frequency. The three loci cooperate to the risk that is low in subjects carrying no homozygous genotype (O.R. 1.25) but it is very high (O.R. 13.240) in subjects carrying the three homozygous genotypes.From a practical point of view, the study of ADA gene may help to detect obese subjects at high risk of T2D who need active preventive measures. The results point to the importance of further studies on the role of genetic variability within ADA gene on the relationship within obesity and T2D

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