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.

1.
Cristalli G, Costanzi S, Lambertucci C, Lupidi G, Vittori S, Volpini R, Camaioni E: Adenosine deaminase: functional implications and different classes of inhibitors. Med Res Rev 2001;21:105–128.
2.
Moriwaki Y, Yamamoto T, Higashino K: Enzymes involved in purine metabolism-a review of histochemical localization and functional implications. Histol Histopathol 1999;14:1321–1340.
3.
Franco R, Casado V, Ciruela F, Saura C, Mallol J, Canela EI, Lluis C: Cell surface adenosine deaminase: much more than an ectoenzyme. Prog Neurobiol 1997;52:283–294.
4.
Hirschhorn R, Yang DR, Israni A: An Asp8Asn substitution results in the adenosine deaminase (ADA) genetic polymorphism (ADA 2 allozyme): occurrence on different chromosomal backgrounds and apparent intragenic crossover. Ann Hum Genet 1994;58:1–9.
5.
Battistuzzi G, Iudicone P, Santolamazza P, Petrucci R: Activity of adenosine deaminase allelic forms in intact erythrocytes and in lymphocytes. Ann Hum Genet 1981;45:15–19.
6.
Weissmann J, Vollmer M, Pribilla O: Survey of the distribution of adenosine deaminase and superoxide dismutase markers in different populations. Hum Hered 1982;32:344–356.
7.
Barankiewicz J, Danks AM, Abushanab E, Makings L, Wiemann T, Wallis RA, Pragnacharyulu PV, Fox A, Marangos PJ: Regulation of adenosine concentration and cytoprotective effects of novel reversible adenosine deaminase inhibitors. J Pharmacol Exp Ther 1997;283:1230–1238.
8.
Loh E, Rebbeck TR, Mahoney PD, DeNofrio D, Swain JL, Holmes EW: Common variant in AMPD1 gene predicts improved clinical outcome in patients with heart failure. Circulation 1999;99:1422–1425.
9.
Anderson JL, Habashi J, Carlquist JF, Muhlestein JB, Horne BD, Bair TL, Pearson RR, Hart N: A common variant of the AMPD1 gene predicts improved cardiovascular survival in patients with coronary artery disease. J Am Coll Cardiol 2000;36:1248–1252.
10.
Guo SW, Thompson EA: Performing the exact test of Hardy-Weinberg proportion for multiple alleles. Biometrics 1992;48:361–372.
11.
Bottini E, Gloria-Bottini F: Adenosine deaminase and body mass index in non-insulin-dependent diabetes mellitus. Metabolism 1999;48:949–951.
12.
Bottini N, De Luca D, Saccucci P, Fiumara A, Elia M, Porfirio MC, Lucarelli P, Curatolo P: Autism: evidence of association with adenosine deaminase genetic polymorphism. Neurogenetics 2001;3:111–113.
13.
Bottini N, Gloria-Bottini F, Amante A, Saccucci P, Bottini E: Genetic polymorphism and Th1/Th2 orientation. Int Arch Allergy Immunol 2005;138:328–333.
14.
Nicotra M, Bottini N, Grasso M, Gimelfarb A, Lucarini N, Cosmi E, Bottini E: Adenosine deaminase and human reproduction: a comparative study of fertile women and women with recurrent spontaneous abortion. Am J Reprod Immunol 1998;39:266–270.
15.
Jackson EK, Koehler M, Mi Z, Dubey RK, Tofovic SP, Carcillo JA, Jones GS: Possible role of adenosine deaminase in vaso-occlusive diseases. J Hypertens 1996;14:19–29.
16.
Moskvina V, Holmans P, Schmidt KM, Craddock N: Design of case-controls studies with unscreened controls. Ann Hum Genet 2005;69:566–576.
17.
Willems L, Ashton KJ, Headrick JP: Adenosine-mediated cardioprotection in the aging myocardium. Cardiovasc Res 2005;66:245–255.
18.
Kitakaze M, Minamino T, Node K, Takashima S, Funaya H, Kuzuya T, Hori M: Adenosine and cardioprotection in the diseased heart. Jpn Circ J 1999;63:231–243.
19.
Miura T, Tsuchida A: Adenosine and preconditioning revisited. Clin Exp Pharmacol Physiol 1999;26:92–99.
20.
Ciruela F, Saura C, Canela EI, Mallol J, Lluis C, Franco R: Adenosine deaminase affects ligand-induced signalling by interacting with cell surface adenosine receptors. FEBS Lett 1996;380:219–223.
21.
Heusch G, Schulz R: Endogenous protective mechanisms in myocardial ischemia: hibernation and ischaemic preconditioning. Am J Cardiol 1997;80:26A–33A.
22.
Lankford AR, Yang JN, Rose’Meyer R, French BA, Matherne GP, Fredholm BB, Yang Z: Effect of modulating cardiac A1 adenosine receptor expression on protection with ischaemic preconditioning. Am J Physiol Heart Circ Physiol 2006;290:H1469–H1473.
23.
Hayes ES: Adenosine receptors and cardiovascular disease: the adenosine-1 receptor (A1) and A1 selective ligands. Cardiovasc Toxicol 2003;3:71–88.
24.
McCallion K, Harkin DW, Gardiner KR: Role of adenosine in immunomodulation: review of the literature. Crit Care Med 2004;32:273–277.
25.
Alsene K, Deckert J, Sand P, de Wit H: Association between A2a receptor gene polymorphisms and caffeine-induced anxiety. Neuropsychopharmacology 2003;28:1694–1702.
26.
Hamilton SP, Slager SL, De Leon AB, Heiman GA, Klein DF, Hodge SE, Weissman MM, Fyer AJ, Knowles JA: Evidence for genetic linkage between a polymorphism in the adenosine 2A receptor and panic disorder. Neuropsychopharmacology 2004;29:558–565.
27.
Retey JV, Adam M, Honegger E, Khatami R, Luhmann UF, Jung HH, Berger W, Landolt HP: A functional genetic variation of adenosine deaminase affects the duration and intensity of deep sleep in humans. Proc Natl Acad Sci USA 2005;102:15676–15681.
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