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

Abstract

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 μmol/l (4–7.2); CT: 7 μmol/l (3.9–9.8); TT: 12.1 μmol/l (7.7–13.3)) with an upper age-specific 95th percentile of 8.3 μmol/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 μmol/l (3–23) vs. 5.5 μmol/l (3–8.4); P= 0.0004), and homocysteine concentrations >8.3 μmol/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 μmol/l and the CT genotype of the MTHFR C677T variant are significant risk factors for venous vascular occlusion in children.