The relationship between polymorphisms in the endothelial cell nitric oxide synthase gene and the platelet GPIIIa gene with myocardial infarction andvenous thromboembolism in African Americans

Study objectives: To determine whether the polymorphic dinucleotide repeats found in intron 4 of the endothelial cell nitric oxide synthase (ecNOS) ge ne and the platelet GPIIIa PLA(1)/A(2) polymorphism are associated with myo cardial infarction (MI) and venous thromboembolism (VTE) in African America ns. Because these two genes may interact physiologically, the third objecti ve was to determine if there was a relationship between the polymorphisms w ith respect to MI and VTE, Design: A hospital-based case-control study. After informed consent was obt ained, blood used for DNA extraction was drawn from the subjects. Setting: The study was conducted in the Anticoagulant: Clinic and the Cardi ology Clinic at Grady Memorial Hospital in Atlanta Georgia. Patients: Subjects were recruited from African-American patients with a rep orted history of MI (n = 110) or VTE (n = 91). Control subjects (n = 185) w ithout a history of cardiovascular or venous disease were recruited from an outpatient clinic. Measurements aid results: The 393 ecNOS allele was more common among MI cas es (36%; p = 0.01) and VTE cases (35%; p = 0.04) than among control subject s (26%). There was no association between the GPIIIa genotypes and either M I or VTE. However, among the MI subjects, there was a strong association be tween the ecNOS 393/393 genotype and the PIA2 allele. It was also found tha t 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 PIA2 allele was significantly asso ciated 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 PIA2 allele was also highly associated with MI. The frequency of the 393 allele was significantly high er in African Americans than what has been reported for other populations. This study furthers not only extends the association of the 393 allele to V TE but has demonstrated an interaction with the PIA2 allele with respect to MI.