The Detection And Meanings Of MTHFR C677T Mutation, Plasma Homocysteine, Serum Folate And Vitamin B₁₂ Levels In BCS Patients

Object: Budd-Chiari syndrome (BCS) represents occlusionof hepatic outflow either at the level of the hepatic veins orinferior vena cava. The main clinical signs of it include twocomplications caused by high plessure of the hepatic vein andvena cava. The aetiology of BCS is complicated includinggenetic and circumstantial risk factors. Hypercoagulable statesand local thrombosis in the hepatic outflow are related to BCS.In recent years, Factor V Leiden mutation, prothrombin geneG20210A mutation and N⁵ , N¹⁰-methylenetetrahydrofolatereductase (MTHFR) gene C677T mutation have beenrecognized to be risk factors for thrombosis. Factor V Leidenmutation and prothrombin gene G20210A mutation have beenlinked to BCS. Investigations have shown that MTHFR C677Tmutation plays important roles in the formation of thrombosis.The MTHFR gene C677T mutation produces a restrictionenzyme ( Hinfâ… ) sequence, that is T allele. A C to Tsubstitution at nucleotide 677 in the encoding region of theMTHFR gene convert the codon for alanine to valine in itsprotein products. This defection directly leads to thermolabileMTHFR with decreased activity in the remethylation pathwayof homocysteine and it is responsible for the elevated plasmahomosysteine levels (hyperhomocysteinemia, HH). Folate andVitamin B12 are cofactors of MTHFR and the deficiency ofthese two factors will also lead to HH. HH has been recognizedto be an independent risk factor for thrombosis. It promotes tothrombosis from a number of different ways.Now, there are no data to significant evaluate HH, folate andVitamin B12 levels and the MTHFR C677T mutation in BCSpatients. The purpose of our study is to investigate theprevalence of the MTHFR C677T mutation, plasmahomocysteine, surm folate and Vitamin B12 levels in patientswith BCS and to determine their relationship with BCS, andgive some suggestions for the therapy and precaution of BCS.Method: 41 patients with BCS and 80 normal controls wereexamined for the MTHFR C677T mutation and plasma levels ofhomocysteine with the methods of PCR-RFLP andhigh-performance liquid chromatography with fluorescencedetection respectively. Serum folate and Vitamin B12 levelswere measured by radioimmunoassay (RIA). SAS 6.12 wereapplied for statistical analysis.Results: The mean plasma homocysteine were 21.23±5.32umol/L and 11.35±5.16umol/L in patients with BCS andnormal controls respectively. The mean plasma homocysteinelevel was significantly increased in patients with BCS comparedwith normal controls. P=0.01。HH (>15umol/L) was detected in15 (36.59%) patients and in 14 (17.5%) controls (p=0.02, OR:2.72, 95%CI:1.17-6.32).Mean seurm folate were 6. 95±1.19nmol/L and 7.14±1.52nmol/L in BCS patients and controls respectively. SerumVitamin B12 were 117.12±34.53pmol/L in BCS patients and131.16±42.18pmol/L in normal controls. Both serum folateand VitB12 of patients with BCS were not significantly differentfrom those of controls. In addition, serum folate and VitB12levels showed no significant correlation with the plasma Hcylevels (P>0.05).Three kinds of genotype were found: homozygous mutation(MTHFR 677TT), heterozygous mutation (MTHFR 677CT)and wild genotype (MTHFR 677CC). The prevalence of thethree kinds genotypes were as follows: MTHFR 677TT,21.95%%; MTHFR 677CT46.34%; MTHFR 677CC 31.71% inpatients with BCS and MTHFR 677TT, 10.0%; MTHFR 677CT42.5%; MTHFR 677CC 47.5% in normal controls, respectively.The frequencies of homozygote 677TT and the T allele weresignificantly increased in patients with BCS compared withnormal controls. The relative risk of BCS among the carriers of677TT was significantly increased (p=0.045, odd ratios: 3.2995%CI:1.08-10.02). The frequency of heterozygote 677CT inBCS was slightly higher but not significantly increased.Relative risk OR of BCS was 1.63 (95%CI:0.71-3.76) for theheterozygous 677CT genotype.Conclusion: The mean plasma homocysteine level wassignificantly increased in patients with BCS, and the HH was...