ADA*2 Allele of the Adenosine Deaminase Gene May Protect against Coronary Artery Disease

Abstract

Background/Aims: The common G22A polymorphism in the adenosine deaminase (ADA) gene leads to substitution Asp8Asn. The lower activity of the enzyme encoded by A22 (ADA*2) allele may increase tissue concentrations of adenosine, a potent cardioprotective agent. In a case-control study, we investigated the association between ADA polymorphism and coronary artery disease (CAD). Methods: A hundred and seventy-one CAD patients from the north-western part of Poland and 200 consecutive newborns from the same population were genotyped by PCR-RFLP. Results: Twenty-five ADA*1/*2 heterozygotes (12.5%) and 2 ADA*2/*2 homozygotes (1%) were found in the control group, while only 10 *1/*2 heterozygotes (5.9%) and no *2/*2 homozygotes were found in the CAD group. Frequencies of ADA*2 carriers (5.9% vs. 13.5%, p = 0.015) and ADA*2 allele (2.9% vs. 7.3%, p = 0.0083) were lower in CAD patients than in controls. Among CAD patients, a significantly lower proportion of *2 allele carriers was treated with diuretics and ACE inhibitors when compared to *1/*1 wild-type homozygotes. Conclusion: ADA*2 allele may decrease genetic susceptibility to CAD. ADA should be added to the list of candidate genes modifying the risk of cardiovascular diseases.

Lack of association of the G22A polymorphism of the ADA gene in patients with ankylosing spondylitis

“…Evidence suggests that ADA*02 exerts a protective effect in inflammatory diseases such as asthma (Liu et al, 2006) and coronary artery disease (Safranow et al, 2007). Additionally, the haplotype 2 2 /6 1 of ADA, which contains ADA*02, seems to exert protective action against type 1 diabetes in men .…”

“…To characterize the G22A polymorphism of ADA and identify ADA*01 and ADA*02, we used a published polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocol (Safranow et al, 2007). Briefly, an amplified fragment of the ADA gene with primers (sense: 5ꞌ-GCCCGGCCCGTTAAGAAGAGC-3ꞌ; anti-sense: 5ꞌ-GGTCAAGTCAGGGGCAGAAGCAGA-3ꞌ) containing 397 bp was digested using TaqI restriction enzyme, generating 2 fragments for ADA*1 (152 and 245 bp) or an undigested fragment (397 bp) for ADA*2.…”

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.…”

"Avaliação dos polimorfismos nos genes enzima conversora de angiotensina e adenosina deaminase em pacientes com diabetes melito tipo 2"

“…O fragmento amplificado foi então digerido com a enzima de restrição TaqI, específica para a identificação dos alelos ADA*1 e ADA*2. Posteriormente à digestão enzimática, o produto obtido foi submetido à eletroforese em gel de agarose a 1,5% e coloração com brometo de etídeo, que permitiu a visualização em iluminação UV e determinação dos polimorfismos dos fragmentos de restrição, de acordo com metodologia descrita por Safranow et al, (2007). (Apêndice 5) Iniciadores:…”

“…As frequências alélicas e genotípicas encontradas são semelhantes aos estudos de Safranow et al, (2007), na população polonesa e Liu et al, (2006) Ainda não se sabe corretamente quais os mecanismos pelo qual a ADA relacionase ao DM, apenas sabemos que sua atividade apresenta-se elevada em pacientes com essa doença. Kurtul et al, (2004) relataram que a adenosina age diretamente estimulando a atividade da insulina em diversos tecidos, o que diminuiria a intolerância à glicose.…”