Tissue-type plasminogen activator -7,351C/T enhancer polymorphism is associated with a first myocardial infarction.

• We recently identified a polymorphic Sp1 binding site in an enhancer at the tissue-type plasminogen activator (tPA) locus (tPA -7,351C/T), which was associated with vascular tPA release. Subjects homozygous for the -7,351C allele had twice the tPA release rate compared to subjects carrying the -7,351T allele. In this study we tested the hypothesis that the tPA -7,351C/T polymorphism is associated with myocardial infarction (MI). In a population-based prospective nested case-control study within northern Sweden, genotypes were determined among 61 MI cases and 120 controls. In a multivariate model, the tPA -7,351C/T polymorphism (OR 2.68 for T allele carriers; 95% CI 1.31-5.50), tPA antigen (OR 1.16; 95% CI 1.07-1.25) and apo A-I (OR, 0.997; 95% CI 0.995-0.999) were independently associated with a first MI. These findings suggest that genetic markers of local tPA release and circulating steady-state tPA levels carry independent prognostic information.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Keyword

Apolipoprotein A-I

analysis

Binding Sites

Cardiovascular Diseases

epidemiology

Case-Control Studies

Enhancer Elements (Genetics)

genetics

Female

Genetic Predisposition to Disease

Health Surveys

Humans

Hypertension

epidemiology

Intervention Studies

Male

Middle Aged

Multivariate Analysis

Myocardial Infarction

epidemiology

genetics

Obesity

epidemiology

Odds Ratio

Plasminogen Activator Inhibitor 1

analysis

Polymorphism

Genetic

Prognosis

Prospective Studies

Risk

Risk Factors

Sp1 Transcription Factor

metabolism

Sweden

epidemiology

Tissue Plasminogen Activator

genetics

secretion

Publication and Content Type

ref (subject category)

art (subject category)