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

Abstract

Background: Adenosine deaminase (A DA) str uctural gene consists of 12 exons. A number of common variants have been found within the coding and intronic region of the gene: the possible role of this variability on A DA function are unknown. In the present study we reexamined our data on a set of immune related diseases [Type 1 Diabetes (T1D), Rheumatoid Arthritis (RA), Endometriosis (ENDO) and Non Diabetic Coronary Artery Diseases (NDCAD)] investigating with a new approach the relevance of A DA genetic variability on susceptibility to these disorders. Methods: Thr ee single nucleotide polymor phisms were considered, namely Taq1 site (A DA 1 , nt 4050-4053, exon 1), Pst1 site (A DA 2 , nt 19465-19470, intron 2) and MLu NI (A DA 6, nt 31230-31235, exon 6). We reanalyzed the data on 199 children with T1D, on 79 subjects with RA, on 98 women with ENDO, on 136 NDCAD and on 246 healthy blood donors. A DA genotype was determined by restriction fragment length polymorphism (RFLP) analysis. The subjects were classified according to the number of homozygous genotypes for the more frequent alleles at the three loci. All subjects were from White population of Rome. Results: All diseases show a str ong excess of subjects with the more frequent genotype in all loci as compared to controls suggesting a protective effect of heterozygosity within the ADA gene. Conclusions: The data suggest that the combination of polymorphic sites within the A DA gene influences the susceptibility to some immune related disorders and calls for further studies on the relationship between A DA gene structure and immune functions.