A study of three polymorphic sites of the ADA gene in children with type 1 diabetes mellitus.

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 1 , ADA 2 , ADA 6 ) 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 1 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 1 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.