TO THE EDITOR:
In western countries, acute myocardial infarction and ischemic stroke are the most common causes of illness and death. Classic risk factors and lifestyle account only in part for the likelihood of ischemic events [1]. The familial aggregation of coronary heart disease is related largely to the clustering of cardiovascular risk factors. It is well recognized that a history of parental coronary heart disease is associated with increased risk for myocardial ischemia [2]. Low fibrinolytic activity is related to increased plasma levels of plasminogen activator inhibitor-1 (PAI-1) and has been documented in persons who later develop myocardial infarction [3]. Recently, a deletion/insertion polymorphism (4G/5G) within the PAI-1 gene locus was shown to influence the expression of this gene [4]. We have investigated the relation between the PAI-1 4G/5G polymorphism in 1179 healthy persons (514 men and 665 women) and the occurrence of coronary artery disease in their first-degree relatives. All participants (mean age, 37.7 years [range, 22 to 66 years]) and their parents were white and had been living in the same area. A family history of ischemic heart disease was assessed by a modified World Health Organization questionnaire. Polymerase chain reaction and endonuclease digestion were used to evaluate PAI-1 4G/5G polymorphism [5]. The group with a first-degree relative (n = 198) who had a coronary ischemic episode had more homozygotes for the deleted allele (4G/5G) than did the group without such a family history (n = 981) (odds ratio, 1.62 [95% CI, 1.17 to 2.25]; P = 0.005). The frequency of the 4G allele was also abnormally high (odds ratio, 1.29 [CI, 1.04 to 1.60]; P = 0.025). These data support the possibility that the 4G variant of the PAI-1 4G/5G polymorphism is a genetically transmissible coronary risk factor. This polymorphism may explain part of the risk for coronary artery disease related to family history.
1. Tuomiletho J, Kuulasmaa K. The WHO MONICA project. Assessing CHD mortality and morbidity. Int J Epidemiol. 1989; 18:S38-S45.
2. Sing CF, Moll PP. Genetics of variability of CHD risk. Int J Epidemiol. 1989; 18(Suppl 1):S183-95.
3. Hamsten A, De Faire U, Walldius G, Dahlen G, Szamosi A, Landou C, et al. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet. 1987; 2:3-9.
4. Dawson SJ, Wiman B, Hamsten A, Green F, Humphries S, Henney AM. The two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene respond differently to interleukin-1 in HepG2 cells. J Biol Chem. 1993; 268:10739-45.
5. Margaglione M, Grandone E, Cappucci G, Colaizzo D, Giuliani N, Vecchione G, et al. An alternative method for PAI-1 promoter polymorphism (4G/5G) typing. Thromb Haemost. 1997; 77:605-6.
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