Reshetniak T M, Patrushev L I, Tikhonova T F, Kovalenko T F, Mach E S, Aleksandrova E N, Miroshnikov A I, Nasonova V A
Ter Arkh. 2002;74(5):28-32.
To study prevalence of mutation C677T in gene 5.10-MTHFR in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) as well as in persons free of symptoms of systemic diseases of the connective tissue.
85 patients participating in the study were divided into three groups: those with SLE (n = 17), with SLE + APS (n = 42), with primary APS (n = 26). The control group consisted of 30 persons without SLE or APS. 55% of the examinees had thrombotic complications of different location. The diagnosis of the mutation was made using DNA isolated from the peripheral blood with standard methods and polymerase chain reaction. Allele (homozygous or heterozygous) condition of the mutation was confirmed by means of allele-specific primers.
Mutation C677T in MTHFR gene was found in 40 of 85 patients (47%); 11(27.5%) had a homozygous variant, 29(72.5%)--heterozygous. C677T mutation occurred in 5 of 17 SLE patients (29%), it was in all the cases heterozygous. In primary and secondary APS mutation was detected in 51.5% (35 of 68 patients). Recurrent thrombosis occurred more frequently in patients with mutation MTHFR. Three and more episodes of thrombosis were registered in 17 of 40 patients with mutation C677T against 9 of 44 patients without the mutations (p = 0.04).
Relationship between elevated blood levels of APL and MTHFR mutation points to the fact that this genetic marker is an additional thrombogenic factor in APS. Mutation C677T in MTHFR gene in APS patients correlates with recurrent thrombosis.
研究系统性红斑狼疮（SLE）、抗磷脂综合征（APS）以及无系统性结缔组织病症状人群中5,10 -亚甲基四氢叶酸还原酶（MTHFR）基因C677T突变的发生率。
参与研究的85例患者分为三组：SLE患者（n = 17）、SLE + APS患者（n = 42）、原发性APS患者（n = 26）。对照组由30例无SLE或APS的个体组成。55%的受检者有不同部位的血栓形成并发症。采用标准方法从外周血中提取DNA并通过聚合酶链反应进行突变诊断。通过等位基因特异性引物确定突变的等位基因（纯合或杂合）状态。
85例患者中有40例（47%）检测到MTHFR基因C677T突变；11例（27.5%）为纯合变异，29例（72.5%）为杂合变异。17例SLE患者中有5例（29%）发生C677T突变，均为杂合子。原发性和继发性APS患者中突变检出率为51.5%（68例患者中的35例）。MTHFR突变患者复发性血栓形成更为常见。40例C677T突变患者中有17例发生3次及以上血栓形成事件，而44例无突变患者中有9例发生，差异有统计学意义（p = 0.04）。
抗磷脂抗体（APL）水平升高与MTHFR突变之间的关系表明，该遗传标记是APS中一个额外的血栓形成因素。APS患者中MTHFR基因C677T突变与复发性血栓形成相关。
