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

被引:86
作者
Hooper, WC
Lally, C
Austin, H
Benson, J
Dilley, A
Wenger, NK
Whitsett, C
Rawlins, P
Evatt, BL
机构
[1] Ctr Dis Control & Prevent, Hematol Dis Branch, Div AIDS STD & TB Lab Res, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
[2] Emory Univ, Sch Publ Hlth, Atlanta, GA 30322 USA
[3] Emory Univ, Sch Med, Dept Med, Atlanta, GA 30322 USA
[4] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA
[5] Grady Mem Hosp, Atlanta, GA 30335 USA
[6] Emory Univ, Crawford Long Hosp, Atlanta, GA 30365 USA
关键词
African Americans; endothelial cell nitric oxide synthase; glycoprotein IIb/IIIa receptor; myocardial infarction; venous thrombosis;
D O I
10.1378/chest.116.4.880
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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 PLA(1)/A(2) 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 aid 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 PIA2 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 PIA2 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 PIA2 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 PIA2 allele with respect to MI.
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收藏
页码:880 / 886
页数:7
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