[Lowering high levels of fasting total homocysteine with folic acid and vitamins B in patients with venous thromboembolism: relationship between response and the C677T methylenetetrahydrofolate reductase (MTHRF) genotype].
BACKGROUND
High levels of plasma total homocysteine (tHcy) are involved in arterial or venous occlusive diseases. It essentially depends on the nutritional status of folic acid (FA) and vitamins B12 or B6, but also on the methylenetetrahydrofolate reductase (MTHFR) enzymatic activity. We aim to evaluate the response of the hyperhomocysteinemia (HHcy) to a standard schedule of vitamin supplementation, according with the MTHFR genotype.


METHODS
227 patients, diagnosed with venous thromboembolism (VTE) were analysed for tHcy (in fasting conditions), and for the MTHFR-C677T gene polymorphism. When the tHcy exceeded the cut-off point (men = 16, women = 15 mumol/l), the patients were supplemented with a dose equivalent to 1 mg FA, 0.2 mg B12 and 100 mg of B6, daily by 6 weeks. Afterwards they were reanalysed and the reduction was stratified by MTHFR genotype, looking for any difference in the response.


RESULTS
The mean fasting tHcy was 12.3 mumol/l (SD = 8). The 51 hyperhomocysteinemic patients (22%) were older (65.1 y) than the normal ones (55.0 y) (p = 0.0001). The treatment was carried out properly in 46 patients (90%). The pre-treatment mean Hcy was 23.2 (SD = 10.5) mumol/l, and it was reduced to 13.0 (SD = 5.9) (p = 0.0001) (mean reduction = 42.1%). By genotype, the C/C reduced from 21.0 to 13.2 mumol/l (37%) (n = 18), the C/T from 25.0 to 12.6 mumol/l (46%) (n = 24), and the abnormal homozygotes T/T from 22.7 to 14.5 mumol/l (39%) (n = 4), although no statistical significant differences were found. In 80% of cases (37/46), tHcy values normalised. A negative correlation (r = -0.471) (p = 0.005) was observed between age and response.


CONCLUSIONS
The FA/B6/B12 based therapy reduces in a simple, quick and effective way (> 40% in 6 weeks) the pathologic tHcy levels on a VTE population and this is not influenced by the MTHFR genotype. As HHcy seems related with recurrences of venous thrombosis, we could speculate if it would be useful to analyse routinely the tHcy, attempting reduction in selected cases.
González Ordóñez
A J
AJ
Servicio de Hematología, Hospital San Agustín, Avilés. jagonzalez@medynet.com
Medina Rodríguez
J M
JM
Fernández Alvarez
C R
CR
Sánchez García
J
J
Fernández Carreira
J M
JM
Alvarez Martínez
M V
MV
Coto García
E
E
D000328:Adult; D004586:Electrophoresis / Q000379:methods; D005260:Female; D005492:Folic Acid / Q000494:pharmacology* / Q000627:therapeutic use*; D015870:Gene Expression / Q000235:genetics*; D005838:Genotype; D006710:Homocysteine / Q000097:blood* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D011736:Pyridoxine / Q000494:pharmacology* / Q000627:therapeutic use*; D012008:Recurrence; D013924:Thrombophlebitis / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D014805:Vitamin B 12 / Q000494:pharmacology* / Q000627:therapeutic use*
D006710:Homocysteine; D005492:Folic Acid; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D011736:Pyridoxine; D014805:Vitamin B 12