Interaction between hyperhomocysteinemia, mutated methylenetetrahydrofolatereductase (MTHFR) and inherited thrombophilic factors in recurrent venous thrombosis.
Venous thrombosis is a multicausal disease involving acquired and genetic factors. In this study we investigated a possible interaction between hyperhomocysteinemia (fasting or postload) and factor V Leiden or prothrombin G20210A on the risk of recurrent venous thrombosis. We also looked at the risk due to mutations in the MTHFR-gene (C677T and A1298C). We performed a case-control study in 171 patients with a history of recurrent venous thrombosis and 461 control subjects from the general population. Hyperhomocysteinemia (fasting or 6 h after an oral methionine load) was defined as a homocysteine concentration above the 90th percentile of the distributions in the control group. The odds ratio (adjusted for age and sex) for recurrent venous thrombosis was 1.8 (95% CI: 1.1 to 3.0) for fasting hyperhomocysteinemia, 5.1 (95% CI: 3.0 to 8.6) for factor V Leiden and 1.8 (95% CI: 0.7 to 4.2) for prothrombin G20210A. We found 14 patients and 3 controls with both hyperhomocysteinemia and factor V Leiden, which yielded an odds ratio of 11.6 (95% CI: 3.2 to 42.5). We found no interaction between hyperhomocysteinemia and prothrombin G20210A. The relative risk for MTHFR 677CT was 1.6 (95% CI: 1.1 to 2.4) and for MTHFR 677TT was 1.4 (95% CI: 0.7 to 2.8). The combined risk for MTHFR 677TT and factor V Leiden was 18.7 (95% CI: 3.3 to 108). We conclude that hyperhomocysteinemia and factor V Leiden are risk factors for recurrent venous thrombosis. The risk of thrombosis appeared high for individuals who had both risk factors.
Keijzer
Miranda B A J
MB
Department of Endocrinology, University Medical Center Nijmegen, 6500 HB Nijmegen, The Netherlands.
den Heijer
Martin
M
Blom
Henk J
HJ
Bos
Gerard M J
GM
Willems
Huub P J
HP
Gerrits
Wim B J
WB
Rosendaal
Frits R
FR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005165:Factor V; D005192:Family Health; D005260:Female; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D016017:Odds Ratio; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D017354:Point Mutation; D011516:Prothrombin / Q000235:genetics; D012008:Recurrence; D012307:Risk Factors; D019851:Thrombophilia / Q000235:genetics*; D020246:Venous Thrombosis / Q000209:etiology*
C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)