A novel polymorphism in intron 1a of the human factor VII gene (G73A): study of a healthy Italian population and of 190 young survivors of myocardialinfarction

We have identified a novel polymorphism located in intron la of the human f actor VII gene, caused by the nucleotide change G to A at position + 73. In a population of 128 healthy individuals from northern Italy, the variant A 73 allele had a frequency of 0.21, whereas the frequency of the previously reported 10 bp insertion allele located at -323 in the promoter region was 0.17 and that of the Q353 allele in the catalytic region of the factor VII gene was 0.20. In 75% of the healthy individuals, the A73 allele was presen t together with the 10 bp insertion and the Q353 alleles, indicating a stro ng linkage disequilibrium. The concomitant presence of A73 with both the 10 bp and the Q353 alleles was associated with the lowest factor VII levels, measured as coagulant activity, activated factor VII and factor VII antigen . The G73A polymorphism was also evaluated in 190 survivors of myocardial i nfarction who had experienced the event before the age of 45 years and in 1 79 individuals with a negative exercise test matched with patients for sex, age and geographical origin. Patients carrying the A73 allele associated w ith lower factor VII levels tended to have a lower risk of myocardial infar ction (adjusted odds ratio 0.54; 95% confidence intervals 0.29-0.99). In co nclusion, we found a novel variant allele in intron la of the human factor VII gene that is often associated in healthy individuals with the 10 bp and Q353 alleles in the promoter and catalytic region of the same gene. This i ntronic mutation, alone or in association with other factor VII gene polymo rphisms, might confer protection against myocardial infarction in the young .