A common mutation in the methylenetetrahydrofolate reductase gene (C677T) increases the risk for deep-vein thrombosis in patients with mutant factor V (factor V: Q 506)

Marco Cattaneo, Michael Y. Tsai, Paolo Bucciarelli, Emanuela Taioli, Maddalena L. Zighetti, Michelle Bignell, Pier Mannuccio Mannucci

Research output: Contribution to journalArticle

156 Citations (Scopus)

Abstract

Hyperhomocysteinemia is a frequent risk factor for deep-vein thrombosis. A common mutation (C677T) in the gene encoding for methylenetetrahydrofolate reductase (MTHFR) is responsible, in the homozygous state, for decreased enzyme activity and mild hyperhomocysteinemia and is associated with increased risk for cardiovascular disease. We studied the prevalence of C677T MTHFR in 77 patients with deep-vein thrombosis and in 154 age- and sex- matched healthy control subjects. In the same individuals, we also evaluated the frequency of the coexistence of C677T MTHFR with mutant factor V:Q 506, a common risk factor for deep-vein thrombosis. Sixteen patients (20.8%) and 35 control subjects (22.7%) were homozygous for the C677T MTHFR mutation (odds ratio [OR]=0.8, 95% confidence interval [CI]=0.4-2.0). Sixteen patients (20.8%) and 4 control subjects (2.6%) had factor V:Q 506; of them, 10 patients and 3 control subjects had isolated factor V:Q 506 (adjusted OR=6.3, 95% CI=1.6-25.3) and 6 patients and 1 control subject also had C677T MTHFR (adjusted OR=17.3, 95% CI=2.0-152.9). The OR for the coexistence of the two mutations was 65% to 75% higher than the expected joint effect calculated by either an additive (OR=6.0) or multiplicative(OR=4.4) model. The homozygous C677T mutation of MTHFR per se is not a risk factor for deep-vein thrombosis but increases the risk associated with factor V:Q 506. Due to the high prevalence of C677T MTHFR, it is likely that previous studies, which did not look for this mutation, overestimated the relative risk of thrombosis associated with factor V:Q 506 alone.

Original languageEnglish
Pages (from-to)1662-1666
Number of pages5
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume17
Issue number9
Publication statusPublished - 1997

Fingerprint

Methylenetetrahydrofolate Reductase (NADPH2)
Factor V
Venous Thrombosis
Odds Ratio
Mutation
Genes
Hyperhomocysteinemia
Confidence Intervals
Healthy Volunteers
Thrombosis
Cardiovascular Diseases
Enzymes

Keywords

  • Deep-vein thrombosis
  • Factor V:Q (or factor V Leiden)
  • Homocysteine
  • Hyperhomocysteinemia
  • Methylenetetrahydrofolate reductase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

A common mutation in the methylenetetrahydrofolate reductase gene (C677T) increases the risk for deep-vein thrombosis in patients with mutant factor V (factor V : Q 506). / Cattaneo, Marco; Tsai, Michael Y.; Bucciarelli, Paolo; Taioli, Emanuela; Zighetti, Maddalena L.; Bignell, Michelle; Mannucci, Pier Mannuccio.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 17, No. 9, 1997, p. 1662-1666.

Research output: Contribution to journalArticle

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abstract = "Hyperhomocysteinemia is a frequent risk factor for deep-vein thrombosis. A common mutation (C677T) in the gene encoding for methylenetetrahydrofolate reductase (MTHFR) is responsible, in the homozygous state, for decreased enzyme activity and mild hyperhomocysteinemia and is associated with increased risk for cardiovascular disease. We studied the prevalence of C677T MTHFR in 77 patients with deep-vein thrombosis and in 154 age- and sex- matched healthy control subjects. In the same individuals, we also evaluated the frequency of the coexistence of C677T MTHFR with mutant factor V:Q 506, a common risk factor for deep-vein thrombosis. Sixteen patients (20.8{\%}) and 35 control subjects (22.7{\%}) were homozygous for the C677T MTHFR mutation (odds ratio [OR]=0.8, 95{\%} confidence interval [CI]=0.4-2.0). Sixteen patients (20.8{\%}) and 4 control subjects (2.6{\%}) had factor V:Q 506; of them, 10 patients and 3 control subjects had isolated factor V:Q 506 (adjusted OR=6.3, 95{\%} CI=1.6-25.3) and 6 patients and 1 control subject also had C677T MTHFR (adjusted OR=17.3, 95{\%} CI=2.0-152.9). The OR for the coexistence of the two mutations was 65{\%} to 75{\%} higher than the expected joint effect calculated by either an additive (OR=6.0) or multiplicative(OR=4.4) model. The homozygous C677T mutation of MTHFR per se is not a risk factor for deep-vein thrombosis but increases the risk associated with factor V:Q 506. Due to the high prevalence of C677T MTHFR, it is likely that previous studies, which did not look for this mutation, overestimated the relative risk of thrombosis associated with factor V:Q 506 alone.",
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