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.
Ladenvall
Per
P
Cardiovascular Institute, Clinical Experimental Research Laboratory, Sahlgrenska University Hospital/Ostra, Göteborg University, Sweden.
Johansson
Lars
L
Jansson
Jan-Håkan
JH
Jern
Sverker
S
Nilsson
Torbjörn K
TK
Tjärnlund
Anna
A
Jern
Christina
C
Boman
Kurt
K
D016632:Apolipoprotein A-I / Q000032:analysis; D001665:Binding Sites; D002318:Cardiovascular Diseases / Q000453:epidemiology; D016022:Case-Control Studies; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006306:Health Surveys; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics*; D009765:Obesity / Q000453:epidemiology; D016017:Odds Ratio; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D011110:Polymorphism, Genetic; D011379:Prognosis; D011446:Prospective Studies; D012306:Risk; D012307:Risk Factors; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013548:Sweden / Q000453:epidemiology; D010959:Tissue Plasminogen Activator / Q000235:genetics* / Q000378:metabolism
D016632:Apolipoprotein A-I; D017395:Plasminogen Activator Inhibitor 1; D016329:Sp1 Transcription Factor; D010959:Tissue Plasminogen Activator