Prevalence of methylenetetrahydrofolate reductase C677T and its association with arterial and venous thrombosis in the Chinese population

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) g ene. 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 throm bosis were controversial and seldom reported in the Chinese population. We investigated the prevalence of MTHFR C677T and prothrombin G20210A genotype s by polymerase chain reaction (PCR) followed by restriction enzyme digesti on 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 norm al controls was 12.3% and 30.7% respectively, similar to that in Caucasians and Japanese. The mutant 677T homozygotes and alleles were more frequent i n 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 6 77TT and 677T were significantly increased [odds ratios: 3.4, 95% confidenc e 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 cerebra l infarction compared with controls (53.9% vs. 36.9%, 0.01 < P < 0.025). Re lative risk of cerebral infarction was 0.96 (95% CI 0.4-2.3) for 677TT homo zygotes and 1.99 (95% CI 1.2-3.4) for 677C/T heterozygotes. However, the di stribution 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 control s. The prothrombin 20210A mutation was not found in any patients or control s. These results demonstrated that MTHFR 677T was associated with DVT and c erebral infarction but was less associated with CAD in the Chinese populati on.