Risk of venous thrombosis in carriers of a common mutation in the homocysteine regulatory enzyme methylenetetrahydrofolate reductase

Idris T. Ocal, Abbas Sadeghi, Richard Press

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21 Citations (Scopus)

Abstract

Background: Elevated levels of homocysteine are an independent risk factor for venous thrombosis. A common mutation in methylenetetrahydrofolate reductase (MTHFR), an enzyme required for efficient homocysteine metabolism, creates a thermolabile (tl-) enzyme with reduced activity that may predispose to hyperhomo-cysteinemia. Methods and Results: To assess whether this common mutation is a risk factor for venous thromboembolism, a polymerase chain reaction-based genotyping assay was used to compare the prevalence of this mutation in a group with thrombosis versus several jcontrol groups. Of the 331 thrombosis subjects, 47% were heterozygous and 11% homozygous for tl-MTHFR. In comparison, heterozygotes constituted 42-47% and homozygotes 15-16% of each of three control groups (totaling 593 subjects). There was no significant difference in the tl-MTHFR homozygote frequency or allele frequency between the thrombosis and control study groups. Although the prevalence of the factor V R506Q (Leiden) mutation causing activated protein C resistance was significantly higher in the thrombosis (19%) than in the control groups (4-9%), the concomitant presence of tl-MTHFR with factor V R506Q did not contribute to any excess thrombotic risk. Conclusions: Although the tl-MTHFR mutation may predispose to hyperhomocysteinemia, a known risk factor for venous thrombosis, this common genotype is not a direct genetic risk factor for venous thrombosis, either alone or in combination with the factor V R506Q mutation.

Original languageEnglish (US)
Pages (from-to)61-68
Number of pages8
JournalMolecular Diagnosis
Volume2
Issue number1
StatePublished - 1997

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Methylenetetrahydrofolate Reductase (NADPH2)
Homocysteine
Venous Thrombosis
Mutation
Thrombosis
Enzymes
Factor V
Homozygote
Control Groups
Activated Protein C Resistance
Hyperhomocysteinemia
Venous Thromboembolism
Heterozygote
Gene Frequency
Genotype
Polymerase Chain Reaction

Keywords

  • Homocysteine
  • Methylenetetrahydrofolate reductase (MTHFR)
  • Risk factors
  • Thrombosis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Risk of venous thrombosis in carriers of a common mutation in the homocysteine regulatory enzyme methylenetetrahydrofolate reductase. / Ocal, Idris T.; Sadeghi, Abbas; Press, Richard.

In: Molecular Diagnosis, Vol. 2, No. 1, 1997, p. 61-68.

Research output: Contribution to journalArticle

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abstract = "Background: Elevated levels of homocysteine are an independent risk factor for venous thrombosis. A common mutation in methylenetetrahydrofolate reductase (MTHFR), an enzyme required for efficient homocysteine metabolism, creates a thermolabile (tl-) enzyme with reduced activity that may predispose to hyperhomo-cysteinemia. Methods and Results: To assess whether this common mutation is a risk factor for venous thromboembolism, a polymerase chain reaction-based genotyping assay was used to compare the prevalence of this mutation in a group with thrombosis versus several jcontrol groups. Of the 331 thrombosis subjects, 47{\%} were heterozygous and 11{\%} homozygous for tl-MTHFR. In comparison, heterozygotes constituted 42-47{\%} and homozygotes 15-16{\%} of each of three control groups (totaling 593 subjects). There was no significant difference in the tl-MTHFR homozygote frequency or allele frequency between the thrombosis and control study groups. Although the prevalence of the factor V R506Q (Leiden) mutation causing activated protein C resistance was significantly higher in the thrombosis (19{\%}) than in the control groups (4-9{\%}), the concomitant presence of tl-MTHFR with factor V R506Q did not contribute to any excess thrombotic risk. Conclusions: Although the tl-MTHFR mutation may predispose to hyperhomocysteinemia, a known risk factor for venous thrombosis, this common genotype is not a direct genetic risk factor for venous thrombosis, either alone or in combination with the factor V R506Q mutation.",
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N2 - Background: Elevated levels of homocysteine are an independent risk factor for venous thrombosis. A common mutation in methylenetetrahydrofolate reductase (MTHFR), an enzyme required for efficient homocysteine metabolism, creates a thermolabile (tl-) enzyme with reduced activity that may predispose to hyperhomo-cysteinemia. Methods and Results: To assess whether this common mutation is a risk factor for venous thromboembolism, a polymerase chain reaction-based genotyping assay was used to compare the prevalence of this mutation in a group with thrombosis versus several jcontrol groups. Of the 331 thrombosis subjects, 47% were heterozygous and 11% homozygous for tl-MTHFR. In comparison, heterozygotes constituted 42-47% and homozygotes 15-16% of each of three control groups (totaling 593 subjects). There was no significant difference in the tl-MTHFR homozygote frequency or allele frequency between the thrombosis and control study groups. Although the prevalence of the factor V R506Q (Leiden) mutation causing activated protein C resistance was significantly higher in the thrombosis (19%) than in the control groups (4-9%), the concomitant presence of tl-MTHFR with factor V R506Q did not contribute to any excess thrombotic risk. Conclusions: Although the tl-MTHFR mutation may predispose to hyperhomocysteinemia, a known risk factor for venous thrombosis, this common genotype is not a direct genetic risk factor for venous thrombosis, either alone or in combination with the factor V R506Q mutation.

AB - Background: Elevated levels of homocysteine are an independent risk factor for venous thrombosis. A common mutation in methylenetetrahydrofolate reductase (MTHFR), an enzyme required for efficient homocysteine metabolism, creates a thermolabile (tl-) enzyme with reduced activity that may predispose to hyperhomo-cysteinemia. Methods and Results: To assess whether this common mutation is a risk factor for venous thromboembolism, a polymerase chain reaction-based genotyping assay was used to compare the prevalence of this mutation in a group with thrombosis versus several jcontrol groups. Of the 331 thrombosis subjects, 47% were heterozygous and 11% homozygous for tl-MTHFR. In comparison, heterozygotes constituted 42-47% and homozygotes 15-16% of each of three control groups (totaling 593 subjects). There was no significant difference in the tl-MTHFR homozygote frequency or allele frequency between the thrombosis and control study groups. Although the prevalence of the factor V R506Q (Leiden) mutation causing activated protein C resistance was significantly higher in the thrombosis (19%) than in the control groups (4-9%), the concomitant presence of tl-MTHFR with factor V R506Q did not contribute to any excess thrombotic risk. Conclusions: Although the tl-MTHFR mutation may predispose to hyperhomocysteinemia, a known risk factor for venous thrombosis, this common genotype is not a direct genetic risk factor for venous thrombosis, either alone or in combination with the factor V R506Q mutation.

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