Gene-gene and gene-environment interactions in mild hyperhomocysteinemia

Armando D'Angelo, Giuseppina Mazzola, Isabella Fermo

Research output: Contribution to journalArticlepeer-review


Mild/moderate hyperhomocysteinemia (HHcy), a highly prevalent condition, is independently associated with an increased risk of arterial and venous thromboembolic diseases. Early reports of the association of mild/moderate HHcy with juvenile venous thromboembolism have shown familiarity for HHcy in relatives of index cases with thrombosis. Similar to inherited thrombophilia defects, inheritance of the HHcy phenotype was accordingly retained important for the definition of HHcy as an independent risk factor for thrombosis. A number of common polymorphisms in genes coding for methylenetetrahydrofolate reductase (MTHFR), methionine-synthase, methionine-synthase reductase and cysthationine β-synthase (CBS) have been explored for their association with homocysteine levels, fasting and post-methionine load, and with thrombotic diseases. MTHFR thermolability accounts for a 10-fold increase in the risk of mild/moderate HHcy. With the possible exception of the CBS 844ins68 insertion, there is no evidence for an increased risk of HHcy for any of these polymorphisms, isolated or in association with MTHFR thermolability. Environmental factors and MTHFR thermolability are main determinants of the HHcy phenotype. If mild/moderate HHcy is a pathogenetic risk factor for thrombosis, intervention aimed to improve the vitamin status appears of major importance, irrespective of common gene polymorphisms of the homocysteine metabolism.

Original languageEnglish
Pages (from-to)337-341
Number of pages5
JournalPathophysiology of Haemostasis and Thrombosis
Issue number5-6
Publication statusPublished - 2003


  • Cysthationine synthase
  • Hyperhomocysteinemia
  • Methionine-synthase
  • Methionine-synthase reductase
  • Methylenetetrahydrofolate reductase
  • Polymorphisms
  • Thrombosis
  • Transcobalamin

ASJC Scopus subject areas

  • Hematology


Dive into the research topics of 'Gene-gene and gene-environment interactions in mild hyperhomocysteinemia'. Together they form a unique fingerprint.

Cite this