A Study of Three Polymorphic Sites of the ADA Gene in Children with Type 1 Diabetes Mellitus

Abstract

Background: Adenosine deaminase is a polymorphic enzyme that has an important role in immune functions and in the regulation of intracellular and extracellular concentrations of adenosine and adenosine receptor activity. Aim: To search for possible association of type 1 diabetes mellitus (DM1) with three loci haplotypes (ADA,, ADA 2 , ADA«) of the adenosine deaminase gene. Patients: One hundred and eighty-nine consecutive children with DM1 from Sassari, Sardinia, and a control sample of 239 children from the same area were studied. Methods: ADA loci genotypes were determined by DNA analysis. Results: Compared to controls, diabetic boys show a decrease of the 2 2 /6* haplotype while diabetic girls show an increase of the same haplotype. This association was replicated in an independent sample from Continental Italy. Conclusions: The 2 2 /6* haplotype may exert a protective action in males but may increase susceptibility to DM1 in females: OR = 0.398, 95% CI 0.16-0.96 for males, and OR = 2.31, 95% CI 1.32-4.06 for females.

Immune Related Diseases and Their Relationship With the Genetic Variability Within the Adenosine Deaminase Gene

“…We have previously performed association studies of ADA gene in T1D, in RA and in CAD. In T1D haplotype differences were observed between T1D children and controls [19]. In CAD differences between patients and controls were also observed [21,22].…”

“…We studied 199 children with Type 1 Diabetes (T1D), 79 subjects with Rheumatoid Arthritis (RA), 98 women with endometriosis, 136 non diabetic subjects with Coronary Artery Disease (CAD) and 246 healthy blood donors (Controls).All subjects were from the White population of Rome. Data on these subjects have been previously reported [18][19][20][21][22]. An analysis on the role of combination of A DA 1 ,ADA 2 and A DA 6 loci ,however, has not been previously performed.…”

Association of Adenosine Deaminase (ADA) +22 G->A (rs73598374) Genotype in Latino Adult Obese

“…There is an association between type 1 diabetes mellitus (DM1) and three alleles (ADA 1 , ADA 2 , ADA 6 ) of the ADA gene. ADA 2/6 alleles may increase susceptibility to DM1 in females [15]. The role of ADA has been implicated as an important regulator of insulin action and in the pathogenesis of diabetes mellitus.…”

Mini Review From the Molecular Base to the Diagnostic Value of Adenosine Deaminase

“…Under physiologic conditions, concentrations of adenosine in extracellular fluid vary from 40-600 nM and downstream effects of ADA signaling include regulation of a variety of homeostatic and adaptive functions (25). However, under some pathologic conditions adenosine levels are elevated, since ADA activity varies in many diseases, particularly in those associated with the immune system such as rheumatoid arthritis (20), cancers (26), diabetes (27), fertility (28), coronary artery disease (29), autism (19), and obesity (30). In conclusion, recent investigations suggest that ADA could play a role in initiation or progression of some diseases.…”