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


OBJECTIVE
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<or=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.
1st Department of Coronary Artery Disease, Institute of Cardiology, Warsaw, Poland. mspiewak@ikard.pl
Mateusz
M
Spiewak
Łukasz A
ŁA
Małek
Grazyna
G
Kostrzewa
Bartłomiej
B
Kisiel
Agnieszka
A
Serafin
Krzysztof J
KJ
Filipiak
Rafał
R
Płoski
Grzegorz
G
Opolski
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000235:genetics*; D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000235:genetics* / Q000628:therapy; D000208:Acute Disease; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001792:Blood Platelets / Q000502:physiology; D000077144:Clopidogrel; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D010979:Platelet Function Tests; D011110:Polymorphism, Genetic / Q000187:drug effects; D018570:Risk Assessment; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine