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CLINICAL RESEARCH: GENETICS

Genotypes associated with myocardial infarction risk are more common in African Americans than in European Americans

David E. Lanfear, MD^*, Sharon Marsh, PhD^*, Sharon Cresci, MD^*, William D. Shannon, PhD^*, John A. Spertus, MD, FACC and Howard L. McLeod, PharmD^*,*

^* Washington University School of Medicine, Departments of Medicine, Genetics, Molecular Biology, and Pharmacology, and Division of Biostatistics, St. Louis, Missouri, USA
Mid America Heart Institute-University of Missouri Kansas City, Kansas City, Missouri, USA

Manuscript received December 15, 2003; revised manuscript received March 5, 2004, accepted March 23, 2004.

^* Reprint requests and correspondence: Dr. Howard L. McLeod, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8069, St. Louis, Missouri 63110-1093, USA.
hmcleod{at}im.wustl.edu

OBJECTIVES: This study was designed to describe the frequencies of multiple myocardial infarction (MI) risk-associated genotypes among different racial groups.

BACKGROUND: Racial disparities in the prevalence of cardiovascular disease (CVD) are well known. Recent large Japanese case-control studies identified connexin-37 (GJA-4), plasminogen activator inhibitor-1 (PAI-1), and stromelysin-1 (MMP-3) polymorphisms as risk factors for MI, but the prevalence of these genotypes among different racial groups in the U.S. needs to be determined.

METHODS: Genomic deoxyribonucleic acid from 95 healthy African Americans (AA) and 95 healthy European Americans (EA) was used for genotyping. Deoxyribonucleic acid containing the region of interest was amplified using the polymerase chain reaction, followed by genotyping using pyrosequencing.

RESULTS: All three MI-risk genotypes were observed in both populations and were in Hardy-Weinberg equilibrium. The frequencies of two of the three "risk-associated" genotypes were significantly higher in the AA population: GJA4 C1019T T/T: AA, 20%, EA, 7% (p = 0.053); MMP3 –1171delA A/A: AA, 78%, EA, 24% (p < 0.001); PAI-1 –668delG G/G: AA, 55%, EA, 16% (p < 0.001). The likelihood of two or more high-risk genotypes was 3.3% among EA subjects and 51% in the AA group (p < 0.001). We found that 9.1% of AA had all three high-risk genotypes, compared with 0% among the EA group (p = 0.0097).

CONCLUSIONS: We found higher frequencies of disease-associated genotypes in AA than in EA. Our results also show that more AA than EA carry multiple risk-associated genotypes. Future studies need to assess whether such genetic profiles predict adverse outcomes in U.S. populations and contribute to racial disparities in CVD burden.

Abbreviations and Acronyms   AA = African Americans   CHD = coronary heart disease   CVD = cardiovascular disease   DNA = deoxyribonucleic acid   EA = European Americans   GJA-4 = connexin-37   MI = myocardial infarction   MMP-3 = stromelysin-1   PAI-1 = plasminogen activator inhibitor-1   PCR = polymerase chain reaction   SNP = single nucleotide polymorphism

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