The 677T genotype of the common MTHFR thermolabile variant and fasting homocysteine in childhood venous thrombosis

Controlled data on the association of MTHFR genotypes, hyperhomocysteinaemia and their interaction with factor V G1691A with childhood thrombosis are not yet available. Therefore we conducted a case-control study comparing 141 childhood patients with venous thrombosis with 345 healthy controls. The MTHFR C677T genotypes, FV G1691A and prothrombin G20210A were evaluated; in addition, fasting homocysteine concentrations were measured in a subgroup of 60 children and 80 healthy controls. 10.4% of the healthy control population showed the MTHFR TT genotype, 34.2% the CT genotype and 55.4% the CC variant. MTHFR genotypes account for fasting homocysteine concentrations in healthy controls (CC: 5.5 mu mol/l (4-7.2); CT: 7 mu mol/l (3.9-9.8); TT: 12.1 mu mol/l (7.7-13.3)) with an upper age-specific 95th percentile of 8.3 mu mol/l. The following frequencies (patients versus controls), odds ratios (OR) and 95% confidence intervals (CI) were found for single defects: MTHFR 677TT genotype (10.6% vs. 10.4%; OR/CI: 1.02/0.54-1.93; P = 0.99) and CT genotype (43.8% vs. 34.2%; OR/CI: 2.12/1.42-3.16; P = 0.0000). A combination of FV G1691A mutation and MTHFR 677CT genotype was found in 9.9% of patients and in 2.9% of the controls (OR/CI: 3.8/1.64-8.75; P = 0.027). Fasting homocysteine median (range) concentrations in the patient group were significantly higher than in the controls (7 mu mol/l (3-23) vs. 5.5 mu mol/l (3-8.4); P = 0.0004), and homocysteine concentrations >8.3 mu mol/l were found in 40% of patients vs. 2.5% of the controls (OR/CI: 22/2.64-183; P = 0.0003). Conclusion Data of this childhood case-control study suggest that mildly elevated fasting homocysteine concentrations > 8.3 mu mol/l and the CT genotype of the MTHFR C677T variant are significant risk factors for venous vascular occlusion in children.