The PAI-1 gene locus 4G/5G polymorphism is associated with a family history of coronary artery disease.
A family history of ischemic events is a major determinant of coronary artery disease (CAD). Plasma levels of plasminogen activator inhibitor 1 (PAI-1) modulate this risk. A deletion/insertion polymorphism within the PAI-1 locus (4G/5G) affects the expression of this gene. We investigated the relationship between the PAI-1 4G/5G polymorphism in 1179 healthy employees of our institution and the occurrence of CAD in their first-degree relatives. A family history of documented ischemic coronary disease was assessed by a modified WHO questionnaire. The PAI-1 4G/5G polymorphism was evaluated by polymerase chain reaction and endonuclease digestion. The group with a first-degree relative who had suffered from a coronary ischemic episode had a higher number of homozygotes for the deleted allele (4G/4G) of the PAI-1 gene compared with subjects without such a family history (odds ratio [OR] = 1.62, 95% confidence interval [CI]=1.17 to 2.25; P=.005). The frequency of the 4G allele was abnormally high as well (OR=1.29, 95% CI=1.04 to 1.60; P=.025). The individuals with a positive family history were older (P<.001) and exhibited a higher body mass index (P=.033) and total cholesterol levels (P<.001) than those without. In a multiple logistic regression analysis, age (P=.006) and PAI-1 4G/4G (P=.024) independently contributed to a family history of coronary heart disease, with 4G/4G carriers exhibiting a more frequent family history of CAD (OR=1.60). The PAI-1 4G/5G polymorphism to some extent thus accounts for the risk of CAD related to a family history for such an event. These findings support the hypothesis that the 4G variant is a transmissible coronary risk factor.
Margaglione
M
M
Unita' di Aterosclerosi e Trombosi and Direzione Sanitaria, IRCCS Casa Sollievo della Sofferenza, S Giovanni Rotondo, Italy.
Cappucci
G
G
Colaizzo
D
D
Giuliani
N
N
Vecchione
G
G
Grandone
E
E
Pennelli
O
O
Di Minno
G
G
D000328:Adult; D000368:Aged; D002874:Chromosome Mapping; D015331:Cohort Studies; D003327:Coronary Disease / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012044:Regression Analysis; D012307:Risk Factors
D017395:Plasminogen Activator Inhibitor 1