THE MUTATION ALA677-]VAL IN THE METHYLENE TETRAHYDROFOLATE REDUCTASE GENE - A RISK FACTOR FOR ARTERIAL-DISEASE AND VENOUS THROMBOSIS

Mild hyperhomocysteinemia has been identified as a risk factor for art erial disease and for venous thrombosis. Individuals homozygous for th e thermolabile variant of the methylene tetrahydrofolate reductase gen e (MTHFR) which results from a common mutation Ala677-->Val and is fou nd in 5-15% of the general population, have significantly elevated pla sma homocysteine levels and may account far one of the genetic risk fa ctors in vascular disease. We have analyzed the prevalence of MTHFR-T homozygotes in patients with arterial disease or venous thrombosis. We studied 191 patients with arterial disease and 127 individuals with v enous thrombosis and compared with 296 unmatched controls. The results showed that there was a high prevalence of homozygotes for the mutate d MTHFR-T allele among a group of patients with arterial disease (19%) in the absence of hyperlipoproteinemia, hypertension, and diabetes me llitus when compared to controls (4%), adds ratio of 5.52 (95% C.I., 2 .27 to 13.51). The prevalence of homozygotes among patients with venou s thrombosis was 11%, odds ratio of 2.93 (95% C.I., 1.23 to 7.01). The risk of venous thrombosis remained high, odds ratio of 2.63, even aft er we excluded 27 patients with hereditary thrombophilia (e.g., factor V Leiden, dysfibrinogenemia, deficiency of protein C, protein S, anti thrombin III, or factor XII) from the 127 overall cases with venous th rombosis. These data support the hypothesis that being a homozygote fo r the MTHFR-T is a risk factor for the development of arterial diaseas e and also for venous thrombosis.