Koch H G, Nabel P, Junker R, Auberger K, Schobess R, Homberger A, Linnebank M, Nowak-Göttl U
Department of Paediatrics, University Hospital, Münster, Germany.
Eur J Pediatr. 1999 Dec;158 Suppl 3:S113-6. doi: 10.1007/pl00014332.
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 micromol/l (4-7.2); CT: 7 micromol/l (3.9-9.8); TT: 12.1 micromol/l (7.7-13.3)) with an upper age-specific 95th percentile of 8.3 micromol/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 micromol/l (3-23) vs. 5.5 micromol/l (3-8.4): P = 0.0004), and homocysteine concentrations >8.3 micromol/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 micromol/l and the CT genotype of the MTHFR C677T variant are significant risk factors for venous vascular occlusion in children.
关于亚甲基四氢叶酸还原酶（MTHFR）基因分型、高同型半胱氨酸血症及其与凝血因子V G1691A的相互作用与儿童血栓形成之间关联的对照数据目前尚未可得。因此，我们开展了一项病例对照研究，比较了141例儿童静脉血栓形成患者与345例健康对照。对MTHFR C677T基因分型、凝血因子V G1691A和凝血酶原G20210A进行了评估；此外，还对60例儿童和80例健康对照的亚组测定了空腹同型半胱氨酸浓度。10.4%的健康对照人群表现为MTHFR TT基因型，34.2%为CT基因型，55.4%为CC变异型。MTHFR基因分型可解释健康对照中的空腹同型半胱氨酸浓度（CC：5.5微摩尔/升（4 - 7.2）；CT：7微摩尔/升（3.9 - 9.8）；TT：12.1微摩尔/升（7.7 - 13.3）），年龄特异性的第95百分位数上限为8.3微摩尔/升。对于单一缺陷，发现了以下频率（患者与对照）、优势比（OR）和95%置信区间（CI）：MTHFR 677TT基因型（10.6%对10.4%；OR/CI：1.02/0.54 - 1.93；P = 0.99）和CT基因型（43.8%对34.2%；OR/CI：2.12/1.42 - 3.16；P = 0.0000）。在9.9%的患者和2.9%的对照中发现了凝血因子V G1691A突变与MTHFR 677CT基因型的组合（OR/CI：3.8/1.64 - 8.75；P = 0.027）。患者组的空腹同型半胱氨酸中位数（范围）浓度显著高于对照组（7微摩尔/升（3 - 23）对5.5微摩尔/升（3 - 8.4）：P = 0.0004），40%的患者同型半胱氨酸浓度>8.3微摩尔/升，而对照组为2.5%（OR/CI：22/2.64 - 183；P = 0.0003）。结论 这项儿童病例对照研究的数据表明，空腹同型半胱氨酸浓度轻度升高>8.3微摩尔/升以及MTHFR C677T变异的CT基因型是儿童静脉血管闭塞的重要危险因素。
