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The Relationship Between Polymorphisms in the Endothelial Cell Nitric Oxide Synthase Gene and the Platelet GPIIIa Gene With Myocardial Infarction and Venous Thromboembolism in African Americans^*

^* From the Hematologic Disease Branch (Drs. Hooper, Dilley, and Evatt, and Ms. Benson), Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, Center for Disease Control and Prevention, Atlanta, GA; Rollins School of Public Health of Emory University (Ms. Lally and Dr. Austin), Department of Medicine (Dr. Wenger), and Department of Pathology and Laboratory Medicine (Dr. Whitsett), Emory University School of Medicine, Atlanta, GA; Grady Memorial Hospital (Dr. Wenger and Ms. Rawlins), Atlanta, GA; and Crawford Long Hospital (Dr. Whitsett), Atlanta, GA.

Correspondence to: W. Craig Hooper, PhD, Centers for Disease Control and Prevention, Mailstop D02, 1600 Clifton Rd, NE, Atlanta, GA 30333; e-mail: woh1{at}cdc.gov

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.

Design: A hospital-based case-control study. After informed consent was obtained, blood used for DNA extraction was drawn from the subjects.

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 outpatient clinic.

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 Pl^A2 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 Pl^A2 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 Pl^A2 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 Pl^A2 allele with respect to MI.

Key Words: African Americans • endothelial cell nitric oxide synthase • glycoprotein IIb/IIIa receptor • myocardial infarction • venous thrombosis

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