F. Gloria-Bottini et al. / Health 5 (2013) 166-169
168
vs newborns) and population (b) in non diabetic subjects
shows a lack of interaction in both males and females
suggesting that the relationship between ADA1 and CAD
is similar in the two populations studied. The association
between ADA1 and CAD is very strong in males (χ2 =
20.651, df = 2, p 0.0001, after correction for multi-
ple comparison p < 0.001) but is lacking in females.
Since in the Polish population we had no data on dia-
betic subjects without CAD a similar analysis comparing
CAD diabetics with non-CAD diabetics could not be
performed.
The analysis of interaction among ADA1, gender and
population in CAD diabetics (c) shows no significant
association between ADA1 and gender in both Italian and
Polish populations. On the contrary the same analysis in
CAD non diabetics (d) shows a significant association
between ADA1 and gender that shares a similar pattern in
Italian and Polish populations.
From these analyses it can be safely concluded 1) that
the association between CAD and ADA1 is present in
non diabetic subjects only and 2) that the pattern of as-
sociation in non diabetic CAD subjects depends on gen-
der and it is present and very strong among males only:
OR (ADA12-1 vs ADA11/CAD vs controls) = 0.195;
95% C.I. 0.059 - 0.693 (p = 0.007) in the Italian popula-
tion and OR = 0.163; 95% C.I. 0.047 - 0.630 (p = 0.004)
in the Polish population. For both populations combined
O.R. 0.170 95% C.I. 0.064 - 0.425 (p = 0.00002).
4. DISCUSSION
Since a number of newborns will suffer CAD later in
their life, it could be objected that these infants do not
represent a reliable control for our study. However, as-
suming that a given genotype is more susceptible with
respect to other genotypes to CAD, the difference be-
tween cases and newborns would be lower as compared
to the difference between cases and adults without CAD.
Therefore taking newborns as controls the association of
CAD with a given genotype will be underevaluated. If
the association is statistically significant “newborns” can
be considered a reliable control.
The present data collected in two independent White
European populations show that the association between
CAD and ADA1 is present in non diabetic patients only:
moreover such association is present and very marked
among males only. Considering both populations in
males the proportion of genotypes carrying the ADA1*2
allele is much lower among CAD patients than among
controls.
The difference between males and females could be
due to different early fatality rate; such difference, how-
ever, is present in non diabetic but not in diabetic sub-
jects and this seems against such hypothesis. Unfortu-
nately, we have no data on the subjects died during the
early stages of cardiac attack.
The fact that association between CAD and ADA1 is
present in non diabetic subjects only suggests the exis-
tence of different mechanisms leading to CAD. A role of
immunological factors has been suggested for athero-
sclerosis: taking into account the well known role of
ADA1 in immunological diseases, the association of
CAD with ADA1 suggests a prevalent role of immu-
nological factors in the pathogenesis of coronary artery
atherosclerosis in CAD without diabetes. In CAD with
diabetes a role of metabolic factors could be more im-
portant explaining the lack of association with ADA1
polymorphism.
Gender differences in immune diseases are well
documented and it has been suggested that in association
studies concerning immune diseases males and females
should be examined separately [12]. Thus, assuming an
immune component in the association between ADA1
and CAD the differences observed between males and
females are in line with other studies. Hormonal factors
may explain these differences. The immune mechanism,
however, does not exclude a direct role of adenosine as a
cardioprotective agent.
REFERENCES
[1] Safranow, K., Rzeuski, R., Binczak-Kuleta, A., Czyzycka,
E., Skowronek, J., Jakubowska, K., et al. (2007) ADA*2
allele of the adenosine deaminase gene may protect against
coronary artery disease. Cardiology, 108, 275-281.
doi:10.1159/000099096
[2] Banci, M., Saccucci, P., D’Annibale, F., Dofcaci, A.,
Trionfera, G., Magrini, A., et al. (2009) Adenosine deami-
nase genetic polymorphism and coronary artery disease.
Cardiology, 112, 74-75. doi:10.1159/000139954
[3] Spencer, N., Hopkinson, D. and Harris, H. (1968) Adenosin
deaminase polymorphism in man. Annals of Human Ge-
netics, 32, 9-14. doi:10.1111/j.1469-1809.1968.tb00044.x
[4] Honing, J., Martiniuk, F., D’Eustachio, P., Zamfirescu, C.,
Desnick, R., Hirschhorn, K., et al. (1981) Confirmation
of the regional localization of genes for human acid-glu-
cosidase and adenosine deaminase by somatic cell hy-
bridisation. Annals of Human Genetics, 48, 49-56.
doi:10.1111/j.1469-1809.1984.tb00833.x
[5] Yasuda, N., Inoue, T., Horizoe, T., Nagata, K., Minami,
H., Kawata, T., et al. (2003) Functional characterization
of the adenosine receptor contributing to glycogenolysis
and gluconeogenesis in rat hepatocytes. European Jour-
nal of Pharmacology, 459, 159-166.
doi:10.1016/S0014-2999(02)02832-7
[6] Barankiewicz, J., Danks, A.M., Abushanab, E., Makings,
L., Wiemann, T., Wallis, R.A., et al. (1997) Regulation of
adenosine concentration and cytoprotective effects of
novel reversible adenosine deaminase inhibitors. Journal
of Pharmacology and Experimental Therapeutics, 283,
1230-1238.
[7] Ciruela, F., Saura, C., Canela, E.I., Mallol, J., Lluis, C.
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