Study objectives: To determine whether the polymorphic
dinucleotide repeats found in intron 4 of the endothelial cell nitric
oxide synthase (ecNOS) gene and the platelet GPIIIa
PLA1/A2 polymorphism are associated with
myocardial infarction (MI) and venous thromboembolism (VTE) in African
Americans. Because these two genes may interact physiologically, the
third objective was to determine if there was a relationship between
the polymorphisms with respect to MI and VTE.
A hospital-based case-control study. After informed consent was
obtained, blood used for DNA extraction was drawn from the
Setting: The study was conducted in the
Anticoagulant Clinic and the Cardiology Clinic at Grady Memorial
Hospital in Atlanta Georgia.
Patients: Subjects were
recruited from African-American patients with a reported history of MI
(n = 110) or VTE (n = 91). Control subjects (n = 185) without a
history of cardiovascular or venous disease were recruited from an
Measurements and results: The 393
ecNOS allele was more common among MI cases (36%; p = 0.01) and VTE
cases (35%; p = 0.04) than among control subjects (26%). There was
no association between the GPIIIa genotypes and either MI or VTE.
However, among the MI subjects, there was a strong association between
the ecNOS 393/393 genotype and the PlA2 allele. It was also
found that the frequency of the 393 allele was higher in
African-American persons (0.26) compared with what has been reported
for Australian Caucasians (0.14) and Japanese (0.10).
Conclusions: The 393 allele but not the PlA2
allele was significantly associated with both MI and VTE in African
Americans. Homozygosity for the 393 allele was significantly associated
to the diagnosis of MI prior to the age of 45. The combination of the
393 allele and a PlA2 allele was also highly associated
with MI. The frequency of the 393 allele was significantly higher in
African Americans than what has been reported for other populations.
This study furthers not only extends the association of the 393 allele
to VTE but has demonstrated an interaction with the PlA2
allele with respect to MI.