Correspondence

Mutation in the Factor V Gene and the Risk of Myocardial Infarction

N Engl J Med 1995; 333:880-881September 28, 1995

Article

To the Editor:

Ridker and colleagues (April 6 issue)1 demonstrated that the mutation resulting in the substitution of glutamine for arginine at position 506 in the gene coding for coagulation factor V is not associated with an increased risk of myocardial infarction or stroke but is strongly associated with the occurrence of deep venous thrombosis. This study fully confirms the results of three of four previous studies2-5 that assessed the relation between myocardial infarction and this mutation, which is responsible for resistance to activated protein C. In the largest series, there was no statistically significant difference in the prevalence of the factor V mutation between the 609 men who had had myocardial infarction (5.1 percent) and the 692 age-matched controls (4.6 percent).2 Nevertheless, these results cannot be extrapolated to people who are homozygous for this trait. Finally, these results suggest that a local event, such as a plaque rupture that triggers platelets and coagulation factors, may be more important in arterial thrombosis than the existence of a permanent and systemic procoagulant state.

Joseph Emmerich, M.D.
Martine Aiach, Ph.D.
Hôpital Broussais, 75014 Paris, France

5 References

1. 1

   Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. N Engl J Med 1995;332:912-917
   Full Text | Web of Science | Medline

2. 2

   Emmerich J, Poirier O, Evans A, et al. Myocardial infarction, Arg 506 to Gln factor V mutation, and activated protein C resistance. Lancet 1995;345:321-321
   CrossRef | Web of Science | Medline

3. 3

   Marz W, Seydewitz H, Winkelmann B, Chen M, Nauck M, Witt I. Mutation in coagulation factor V associated with resistance to activated protein C in patients with coronary artery disease. Lancet 1995;345:526-526
   CrossRef | Web of Science | Medline

4. 4

   van Bockxmeer FM, Baker RI, Taylor RR. Premature ischaemic heart disease and the gene for coagulation factor V. Nat Med 1995;1:185-185
   CrossRef | Web of Science | Medline

5. 5

   Samani NJ, Lodwick D, Martin D, Kimber P. Resistance to activated protein C and risk of premature myocardial infarction. Lancet 1994;344:1709-1710
   CrossRef | Web of Science | Medline

To the Editor:

Ridker and colleagues determined the frequency of the G1691A mutation in the coagulation factor V gene in case patients and controls from the Physicians' Health Study and found no association between this mutation and the risk of myocardial infarction or stroke, although heterozygous carriers had a nearly threefold increase in the risk of primary venous thrombosis. In a case–control study of 207 patients treated by percutaneous transluminal coronary angioplasty and 480 controls, we also found no association between heterozygosity for the G1691A mutation in the factor V gene and coronary heart disease (frequency of the mutation, 8.2 percent in patients vs. 7.9 percent in controls; P not significant). Similar findings also emerged from a recent prospective study.1

However, Ridker et al. identified no subjects homozygous for the 1691A allele. It may therefore be premature to exclude a role for this mutation in cardiovascular disease. Holm et al. have described two women, 33 and 34 years of age, who were homozygous for the mutation and who had already had myocardial infarctions.2 The single patient in our study who was homozygous for the 1691A allele had a myocardial infarction at the age of 48. His parents and two of his three siblings also died of coronary heart disease. Thus, more data are needed to determine whether homozygosity for the 1691A allele predisposes people to arterial thrombosis.

Juergen Heinrich, Ph.D.
Thomas Budde, M.D.
Gerd Assmann, M.D.
University Hospital Münster, 48129 Münster, Germany

2 References

1. 1

   Emmerich J, Poirier O, Evans A, et al. Myocardial infarction, Arg 506 to Gln factor V mutation, and activated protein C resistance. Lancet 1995;345:321-321
   CrossRef | Web of Science | Medline

2. 2

   Holm J, Zoller B, Svensson PJ, Berntorp E, Erhardt L, Dahlback B. Myocardial infarction associated with homozygous resistance to activated protein C. Lancet 1994;344:952-953
   CrossRef | Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   Herbert H. Watzke. (2003) Clinical significance of gene-diagnosis for defects in coagulation factors and inhibitors. Wiener Klinische Wochenschrift 115:13-14, 475-481
   CrossRef

2. 2

   D. Petrovic, T. Milanez, J. Kobal, D. Bregar, K. P. Potisk, B. Peterlin. (2003) Prothrombotic gene polymorphisms and atherothrombotic cerebral infarction. Acta Neurologica Scandinavica 108:2, 109-113
   CrossRef

3. 3

   J Emmerich, M Alhenc-Gelas, M Aiach, J.N. Fiessinger. (1996) Resistance to activated protein C: role in venous and arterial thrombosis. Biomedicine & Pharmacotherapy 50:6-7, 254-260
   CrossRef