[The thrombin generation is associated with the PIA1/A2 beta3, integrin polymorphism in aspirin-treated patients with coronary artery disease: a role of statins].
BACKGROUND
The PIA2 allele is present in about 20-30% of European population. This allele has been associated with resistance to the antithrombotic action of aspirin in healthy PIA2 carriers.


OBJECTIVE
To evaluate the functional association of the PIA1/A2 polymorphism of beta3 intergrins with increased thrombin generation and platelet activation in patients with coronary artery disease (CAD), treated with low-dose aspirin and whether the effect of this polymorphism is modulated by statin administration.


METHODS
In 31 patients (25 M, 6 F) with CAD, aged 47 to 76 years, the thrombin-antithrombin complex generation (TAT) and the soluble form of CD40 ligand level (sCD40L) in blood collected every 60 seconds at sites of standardized microvascular injury were determined.


RESULTS
Coronary angiography revealed > or = 1 major epicardial artery stenosis (> or = 50%) in all patients. Genotyping determined 18 subjects homozygous for PIA1 and 13 PIA2 heterozygous carriers. Homozygous PIA1 subjects exhibited increased fibrinogen levels compared with PIA2 carriers (4.2 [IQ 2.39] g/l vs. 2.5 [0.73] g/l, p <0.05). Maximal TAT level observed 6 min after microvascular injury was higher in PIA2 carriers (p = 0.01). Maximal sCD40L did not differ between PIA1/A1 subjects and PIA2 carriers. The PIA2 allele did not alter the velocity of TAT production and sCD40L release. The analysis of the area under the concentration vs. time curve for TAT revealed that PIA2 carriers exhibited increased thrombin generation compared with PIA1A1 subjects (by 17.5%, p <0.05). Subjects treated with statins (n = 12) had lower TAT generation and sCD40L release than non-treated (by 20%, p <0.005 and 23%, p <0.005, respectively). This effect was not altered by the PIA2 presence.


CONCLUSIONS
In a model of microvascular injury the PIA1/A2 polymorphism influenced thrombin formation but not platelet activation in CAD patients treated with low-dose aspirin. The PIA2 allele did not alter the beneficial effect of statins on blood coagulation.
Stepień
Ewa
E
Krakowski Szpital Specjalistyczny im. Jana Pawła II, Kraków. estepien@szpitaljp2.krakow.pl
Szułdrzyński
Konstanty
K
Branicka
Agnieszka
A
Stankiewicz
Elzbieta
E
Pazdan
Agnieszka
A
Zieliński
Lukasz
L
Bozek
Maria
M
Tomala
Marek
M
Guzik
Bartłomiej
B
Godlewski
Jacek
J
Pawelec
Tomasz
T
Zmudka
Krzysztof
K
D000368:Aged; D000990:Antithrombin III / Q000378:metabolism; D001241:Aspirin / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects / Q000235:genetics; D001780:Blood Coagulation Tests; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D039661:Integrin beta3 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000378:metabolism; D011110:Polymorphism, Genetic; D013917:Thrombin / Q000096:biosynthesis*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D039661:Integrin beta3; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D005340:Fibrinogen; D010447:Peptide Hydrolases; D013917:Thrombin; D001241:Aspirin