open access

Vol 67, No 8 (2009)
Other
Published online: 2009-09-09
Submitted: 2012-12-28
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Original article
Influence of C3435T multidrug resistance gene-1 (MDR-1) polymorphism on platelet reactivity and prognosis in patients with acute coronary syndromes

Mateusz Śpiewak, Łukasz A. Małek, Grażyna Kostrzewa, Bartłomiej Kisiel, Agnieszka Serafin, Krzysztof J. Filipiak, Rafał Płoski, Grzegorz Opolski
Kardiol Pol 2009;67(8):827-834.

open access

Vol 67, No 8 (2009)
Other
Published online: 2009-09-09
Submitted: 2012-12-28

Abstract


Background: Genetic C3435T polymorphism of the multidrug resistance gene-1 (MDR-1) limits oral bioavailability of clopidogrel and influences prognosis in patients with myocardial infarction.
Aim: To assess the effects of C3435T polymorphism on platelet reactivity and prognosis in patients with acute coronary syndromes treated with percutaneous coronary intervention with stenting.
Methods: Ninety-eight patients were divided into subgroups according to closure time (CT) measured with the Platelet Function Analyzer-100 by means of collagen/adenosine diphosphate (CADP) and collagen/epinephrine (CEPI) cartridges. Patients with CADP-CT < 130 s and patients with CEPI-CT Ł 193 s were defined as non-full responders to antiplatelet therapy. Patients with coexisting polymorphism of P2Y12 and CYP2C19 genes were excluded from the analysis. The primary outcome was the composite of death, non- -fatal myocardial infarction and non-fatal stroke.
Results: Patients carrying the homozygous TT genotype were more likely to have an impaired response to antiplatelet therapy in the test with ADP in comparison to carriers of homozygous CC genotype (OR 5.23; 95% CI 1.34-20.45; p = 0.017). For CT heterozygotes in comparison to CC genotype a weak trend toward non-full response to antiplatelet therapy in the CADP test was observed (OR 2.71; 95% CI 0.80-9.14; p = 0.11). No relationship between MDR-1 C3435T polymorphism and response in CEPI test was observed either for TT homozygotes or for heterozygotes (p = 0.57 and p = 0.55, respectively). During a mean 1.7 years of follow-up no significant difference in the risk of the primary end point was observed.
Conclusions: The C3435T polymorphism of the MDR-1 gene influences ADP dependent platelet reactivity in patients with acute coronary syndrome but does not affect mid-term prognosis in this population.

Abstract


Background: Genetic C3435T polymorphism of the multidrug resistance gene-1 (MDR-1) limits oral bioavailability of clopidogrel and influences prognosis in patients with myocardial infarction.
Aim: To assess the effects of C3435T polymorphism on platelet reactivity and prognosis in patients with acute coronary syndromes treated with percutaneous coronary intervention with stenting.
Methods: Ninety-eight patients were divided into subgroups according to closure time (CT) measured with the Platelet Function Analyzer-100 by means of collagen/adenosine diphosphate (CADP) and collagen/epinephrine (CEPI) cartridges. Patients with CADP-CT < 130 s and patients with CEPI-CT Ł 193 s were defined as non-full responders to antiplatelet therapy. Patients with coexisting polymorphism of P2Y12 and CYP2C19 genes were excluded from the analysis. The primary outcome was the composite of death, non- -fatal myocardial infarction and non-fatal stroke.
Results: Patients carrying the homozygous TT genotype were more likely to have an impaired response to antiplatelet therapy in the test with ADP in comparison to carriers of homozygous CC genotype (OR 5.23; 95% CI 1.34-20.45; p = 0.017). For CT heterozygotes in comparison to CC genotype a weak trend toward non-full response to antiplatelet therapy in the CADP test was observed (OR 2.71; 95% CI 0.80-9.14; p = 0.11). No relationship between MDR-1 C3435T polymorphism and response in CEPI test was observed either for TT homozygotes or for heterozygotes (p = 0.57 and p = 0.55, respectively). During a mean 1.7 years of follow-up no significant difference in the risk of the primary end point was observed.
Conclusions: The C3435T polymorphism of the MDR-1 gene influences ADP dependent platelet reactivity in patients with acute coronary syndrome but does not affect mid-term prognosis in this population.
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Keywords

antiplatelet drugs; acute coronary syndromes; multidrug resistance polymorphism; response variability

About this article
Title

Original article
Influence of C3435T multidrug resistance gene-1 (MDR-1) polymorphism on platelet reactivity and prognosis in patients with acute coronary syndromes

Journal

Kardiologia Polska (Polish Heart Journal)

Issue

Vol 67, No 8 (2009)

Pages

827-834

Published online

2009-09-09

Bibliographic record

Kardiol Pol 2009;67(8):827-834.

Keywords

antiplatelet drugs
acute coronary syndromes
multidrug resistance polymorphism
response variability

Authors

Mateusz Śpiewak
Łukasz A. Małek
Grażyna Kostrzewa
Bartłomiej Kisiel
Agnieszka Serafin
Krzysztof J. Filipiak
Rafał Płoski
Grzegorz Opolski

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