血浆Hcy水平及MTHFR基因C667T突变与肝硬化的相关性研究

Correlation between Plasma Hcy Level and MTHFR Gene Polymorphism with Hepatic Cirrhosis

目的探讨血浆同型半胱氨酸(Hcy)水平与肝硬化的关系及血浆Hcy水平升高的遗传因素。方法采用高效液相色谱法(HPLC)测定64例肝硬化患者、42例非肝硬化肝病患者和60名健康对照者血浆Hcy水平,聚合酶链反应限制性片段长度多态性技术(PCR RFLP)分析N5,N10亚甲基四氢叶酸还原酶(MTHFR)基因C667T突变。结果肝硬化组血浆Hcy水平[(14.6±6.9)μmol/L]显著高于非肝硬化肝病组[(9.3±5.2)μmol/L]和正常对照组[(7.1±3.9)μmol/L](均P<0.01);MTHFR基因677位点碱基变异致3种基因型C/C、C/T和T/T,肝硬化组3种基因型分布频率(18.8%,50.0%,31.2%)明显高于非肝硬化肝病组(45.2%,40.5%,14.3%)和正常对照组(53.3%,33.4%,13.3%)(均P<0.01),非肝硬化肝病组3种基因型分布频率与正常对照组比较,差异无显著性意义(均P>0.05);血浆Hcy水平增高与T/T基因型别相关。结论血浆Hcy水平升高是肝硬化的一个危险因素,可能与MTHFR基因677位点碱基C→T突变有关。

Objective To investigate the relationship between plasma homocysteine （Hcy） level and hepatic cirrhosis and the genetic factor of elevated plasma Hcy level. Methods The plasma Hcy level was determined by means of high performance liquid chromatography （HPi.C） and the gene polymorphism of N^5, N^10 methylenetetrahydrofolate reductase （MTHFR） detected by using PCR restriction fragment length polymorphisms （RFLP） in 64 patients with hepatic cirrhosis, 42 non-cirrhosis patients and 60 healthy controls. Results The plasma Hcy level in the patients with hepatic cirrhosis was （14.6±6.9）μmol/L, markedly higher than that in non-cirrhosis group （9.3±5.2）μmol/L and normal control group （7. 1±3.9）μmol/L （all P〈0.01） . There were 3 geneotypes of C/C, C/T and T/T resulting from base variation of MTHFR gene at locus 677. The frequency of C/C, C/T and T/T in cirrhosis group was 18.8%, 50.0% and 31.2% respectively, signiticantly higher than that in non-cirrhosis group （45.2%, 40.5% and 14.3% respectively） and normal control group （53.3%, 33.4% and 13.3% respectively） （all P〈0.01） . The elevated plasma Hcy level in the patients was correlated with the T/T genotypes. Conclusion The elevated plasma Hcy level was a risk factor for cirrhosis and might related to the C/T mutation at locus 677 of MTHFR gene.