Prothrombotic genetic risk factors in young survivors of myocardial infarction

It has long been thought that an individual thrombotic tendency increases t he risk of myocardial infarction, especially in young adults. Several "prot hrombotic" genetic factors that may influence the individual thrombotic ris k have been identified. To investigate the association between the risk of myocardial infarction at a young age and genetic factors thought to be asso ciated with an increased tendency to thrombosis (the polymorphisms 4G/5G of the PAI-1 gene, PIA1/PIA2 of the platelet glycoprotein IIIa, C3550T of the platelet glycoprotein Ib gene, G10976A of the factor VII gene, C677T of th e methylenetetrahydrofolate reductase gene, G1691A of the factor V gene, an d G20210A of the prothrombin gene), we performed a case-control study evalu ating 200 survivors (185 men, 15 women) of myocardial infarction who had ex perienced the event before the age of 45 years and 200 healthy subjects wit h a negative exercise test, individually matched for sex, age, and geograph ic origin with the cases. The presence of the PIA2 polymorphic allele was t he only prothrombotic genetic factor associated with the risk of myocardial infarction at a young age. The odds ratio for carriers of the PIA2 allele compared with those of the PIA1 allele was 1.84 (95% confidence intervals ( CI) 1.12 to 3.03). There was a significant interaction between the presence of the PIA2 allele and smoking: with their simultaneous presence, 46% (95% confidence intervals 11% to 81%) of premature myocardial infarctions were attributable to the interaction between the two factors. In conclusion, car rying the PIA2 polymorphic allele of platelet glycoprotein IIIa was the onl y genetic prothrombotic factor associated with the risk of developing myoca rdial infarction at a young age. The clinical expression of this genetic pr edisposition seems to be enhanced by smoking. (C) 1999 by The American Soci ety of Hematology.