This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Murphy, R. P. Articles by Fitzgerald, D. J. Search for Related Content PubMed PubMed Citation Articles by Murphy, R. P. Articles by Fitzgerald, D. J. Related Collections Coagulation and fibronolysis Genetics of cardiovascular disease Other Vascular biology

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:266.)
© 2000 American Heart Association, Inc.

Thrombosis

Prospective Evaluation of the Risk Conferred by Factor V Leiden and Thermolabile Methylenetetrahydrofolate Reductase Polymorphisms in Pregnancy

Ronan P. Murphy; Catherine Donoghue; Ruth J. Nallen; Melwyn D’Mello; Carmen Regan; Alexander S. Whitehead; Desmond J. Fitzgerald

From the Department of Clinical Pharmacology (R.P.M., R.J.N., D.J.F.), Royal College of Surgeons in Ireland; the National Maternity Hospital (M.D’M., C.R.); and the Department of Genetics and Biotechnology Institute (C.D., A.S.W.), Trinity College, Dublin, Ireland; and the Department of Pharmacology and Center for Experimental Therapeutics (A.S.W.), University of Pennsylvania Medical School, Philadelphia, Pa.

Correspondence to Professor Desmond Fitzgerald, Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, 123 St. Stephen’s Green, Dublin 2, Ireland. E-mail dfitzgerald{at}rcsi.ie

Abstract—Factor V (FV) Leiden and thermolabile methylenetetrahydrofolate reductase (MTHFR) are 2 common polymorphisms that have been implicated in vascular thrombosis. We determined whether these mutations predicted an adverse outcome in pregnancy. Second, we looked for an interaction between these 2 mutations in patients with recurrent fetal loss or thrombosis in pregnancy. Primigravid subjects at their booking visit to the National Maternity Hospital (Holles Street, Dublin, Ireland) were screened for the polymorphisms. Thermolabile MTHFR and FV Leiden genotypes were detected by either restriction fragment length polymorphism or heteroduplex capillary chromatography. The carrier frequency of FV Leiden in the screened primigravid population was 2.7% (allele frequency 1.36%), all being heterozygous for the mutation. This value was lower than expected from previous studies in European populations. Forty-nine percent of the screened population (289 of 584) were heterozygous for thermolabile MTHFR, and 10.6% were homozygous (62 of 584). The frequency of the 2 polymorphisms was no higher in those who subsequently developed preeclampsia (n=12) or intrauterine growth retardation (n=9), and none of the screened population developed thrombosis. However, the frequency of FV Leiden was higher in patients who subsequently miscarried after the first trimester of pregnancy (allele frequency of 5.5%, P=0.0356). Among those positive for FV Leiden, 3 of 27 miscarried, compared with 24 of 572 of FV Leiden–negative patients (11% versus 4.2%). No interaction was found between the 2 mutations in the control or patient populations. In patients with a prior history of venous thrombosis, the carrier rate of FV Leiden was increased (4 of 33, allele frequency of 7.6%, P=0.0115). In contrast, the carrier frequency for thermolabile MTHFR was no higher, and there was no interaction between the 2 mutations. Neither mutation occurred at a significantly higher frequency in patients with a prior history of recurrent fetal loss. In conclusion, FV Leiden is a risk factor for thrombosis in pregnancy and possibly for second-trimester miscarriage independent of thermolabile MTHFR. However, prospective analysis suggests that the risk conferred by FV Leiden is low in a primigravid population. The thermolabile MTHFR genotype was not implicated in any adverse outcome.

Key Words: factor V Leiden polymorphism • thermolabile methylenetetrahydrofolate reductase polymorphism • pregnancy • venous thrombosis • recurrent fetal loss • genetic risk factors

This article has been cited by other articles:

				S. M. Nelson and I. A. Greer The potential role of heparin in assisted conception Hum. Reprod. Update, November 1, 2008; 14(6): 623 - 645. [Abstract] [Full Text] [PDF]

				L. Sharp, Z. Miedzybrodzka, A. H. Cardy, J. Inglis, L. Madrigal, S. Barker, D. Chesney, C. Clark, and N. Maffulli The C677T Polymorphism in the Methylenetetrahydrofolate Reductase Gene (MTHFR), Maternal Use of Folic Acid Supplements, and Risk of Isolated Clubfoot: A Case-Parent-Triad Analysis Am. J. Epidemiol., November 1, 2006; 164(9): 852 - 861. [Abstract] [Full Text] [PDF]

				S. M. Bates, I. A. Greer, J. Hirsh, and J. S. Ginsberg Use of Antithrombotic Agents During Pregnancy: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 627S - 644S. [Abstract] [Full Text] [PDF]

				G. Kovalevsky, C. R. Gracia, J. A. Berlin, M. D. Sammel, and K. T. Barnhart Evaluation of the Association Between Hereditary Thrombophilias and Recurrent Pregnancy Loss: A Meta-analysis Arch Intern Med, March 8, 2004; 164(5): 558 - 563. [Abstract] [Full Text] [PDF]