Zheng Y Z, Tong J, Do X P, Pu X Q, Zhou B T
Central Laboratory, Department of Neurology and Department of Cardiology, Xiang Ya Hospital, Hunan Medical University, Changsha 410008, PR China.
Br J Haematol. 2000 Jun;109(4):870-4. doi: 10.1046/j.1365-2141.2000.02112.x.
Moderate hyperhomocysteinaemia (MHH) is associated with arterial and venous thrombosis. A main genetic defect related to MHH is a C to T substitution at nucleotide 677 of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. A prothrombin 20210A mutation was recently identified as a risk factor for arterial and venous thrombosis. However, studies on the prevalence of mutant MTHFR C677T and prothrombin G20210A and their association with thrombosis were controversial and seldom reported in the Chinese population. We investigated the prevalence of MTHFR C677T and prothrombin G20210A genotypes by polymerase chain reaction (PCR) followed by restriction enzyme digestion in 420 Chinese subjects: 53 with deep venous thrombosis (DVT); 145 with cerebrovascular disease [115 cerebral infarction, 30 cerebral haemorrhage (CH)]; 100 with coronary artery disease (CAD); and 122 control subjects. The prevalence of the mutated MTHFR 677TT genotype and the 677T allele in normal controls was 12.3% and 30.7% respectively, similar to that in Caucasians and Japanese. The mutant 677T homozygotes and alleles were more frequent in patients with DVT than in controls (18.9% vs. 12.3%, 0.01 < P < 0. 025; 48.1% vs. 30.7%, P < 0.005). The relative risk of DVT among the carriers of 677TT and 677T were significantly increased [odds ratios: 3.4, 95% confidence interval (CI) 1.3-9.5, and 3.6, 95% CI 1. 7-7.7, respectively). The mutant MTHFR heterozygous 677C/T carriers were increased in patients with cerebral infarction compared with controls (53.9% vs. 36.9%, 0.01 < P < 0.025). Relative risk of cerebral infarction was 0.96 (95% CI 0.4-2.3) for 677TT homozygotes and 1.99 (95% CI 1.2-3.4) for 677C/T heterozygotes. However, the distribution of the MTHFR TT genotype was less frequent in patients with CAD with coronary artery stenosis of > 50% than in controls (2. 8% vs. 12.3%, 0.025 < P < 0.05). Relative risk of CAD was not increased among the carriers of 677TT and 677T (odds ratios: 0.2, 95% CI 0-1.1, and 0.97, 95% CI 0.5-1.8, respectively). There were no differences in the distribution of the MTHFR genotypes among CH, CAD with coronary artery stenosis of < 50% and controls. The prothrombin 20210A mutation was not found in any patients or controls. These results demonstrated that MTHFR 677T was associated with DVT and cerebral infarction but was less associated with CAD in the Chinese population.
中度高同型半胱氨酸血症（MHH）与动脉和静脉血栓形成有关。与MHH相关的一个主要基因缺陷是5,10-亚甲基四氢叶酸还原酶（MTHFR）基因第677位核苷酸由C替换为T。最近发现凝血酶原20210A突变是动脉和静脉血栓形成的一个危险因素。然而，关于突变型MTHFR C677T和凝血酶原G20210A的患病率及其与血栓形成的关系的研究存在争议，在中国人群中很少有报道。我们采用聚合酶链反应（PCR）及限制性内切酶消化法，对420名中国受试者进行了MTHFR C677T和凝血酶原G20210A基因型的调查，其中包括53例深静脉血栓形成（DVT）患者、145例脑血管疾病患者[115例脑梗死、30例脑出血（CH）]、100例冠状动脉疾病（CAD）患者和122名对照者。正常对照组中突变型MTHFR 677TT基因型和677T等位基因的患病率分别为12.3%和30.7%，与白种人和日本人相似。DVT患者中突变型677T纯合子和等位基因的频率高于对照组（18.9%对12.3%，0.01<P<0.025；48.1%对30.7%，P<0.005）。677TT和677T携带者发生DVT的相对风险显著增加[优势比分别为：3.4，95%置信区间（CI）1.3 - 9.5，以及3.6，95%CI 1.7 - 7.7]。与对照组相比，脑梗死患者中突变型MTHFR杂合子677C/T携带者增加（53.9%对36.9%，0.01<P<0.025）。677TT纯合子发生脑梗死的相对风险为0.96（95%CI 0.4 - 2.3），677C/T杂合子为1.99（95%CI 1.2 - 3.4）。然而，冠状动脉狭窄>50%的CAD患者中MTHFR TT基因型的分布频率低于对照组（2.8%对12.3%，0.025<P<0.05）。677TT和677T携带者发生CAD的相对风险未增加（优势比分别为：0.2，95%CI 0 - 1.1，以及0.97，95%CI 0.5 - 1.8）。CH、冠状动脉狭窄<50%的CAD患者和对照组之间MTHFR基因型的分布没有差异。在任何患者或对照组中均未发现凝血酶原20210A突变。这些结果表明，在中国人群中，MTHFR 677T与DVT和脑梗死有关，但与CAD的相关性较小。
