肝硬化高同型半胱氨酸血症与MTHFR基因C667T多态性的关系

目的研究肝硬化血浆同型半胱氨酸(HCY)水平及其与N5,N10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性的关系.方法采用柱前衍生化-HPLC方法检测112例健康对照者、87例肝硬化患者血浆同型半胱氨酸的水平,用多聚酶链反应-限制性内切酶片断长度多态性技术(PCR-RFLP)检测其MTHFR基因C667T多态性.结果健康对照组平均血浆HCY浓度为(8.34±3.59)μmol/L,肝硬化组平均血浆HCY浓度为(21.71±4.85)μmol/L.与健康对照组相比,肝硬化组血浆HCY水平显著升高,差异有统计学意义(P＜0.01).PCR-RFLP检测结果发现MTHFR基因型有3种,即纯合子突变TT(+/+)型,杂合子突变TC(+/)型,正常CC(-/-)型.肝硬化组中+/+型、+/型和/-型频率分别为29.9%、52.9%、17.2%;健康对照组分别为19.6%、33.9%、46.4%,两组差异有统计学意义.肝硬化组MTHFR基因突变无论是纯合子还是杂合子突变基因型,其血浆HCY水平均明显高于正常基因型.结论高同型半胱氨酸血症可能是肝硬化的一个危险因素,血浆HCY水平可作为肝硬化的一个辅助诊断指标,MTHFR基因C667T多态性可能是肝硬化高同型半胱氨酸血症的易感基因之一.

The relationship between the plasma homocysteine level and the polymorphism of MTHFR gene C667T in liver cirrhosis

OBJECTIVE: To study the relationship between the plasma homocysteine (HCY) level and the polymorphism of N(5), N(10)-methylenetetrahydrofolate reductase (MTHFR) gene C667T in liver cirrhosis. METHODS: 112 normal subjects and 87 liver cirrhosis patients were recruited in the study. Their plasma HCY levels were measured using high performance liquid chromatography with fluorescence detection and polymorphisms of their MTHFR gene were analyzed using PCR-RFLP. RESULTS: The mean level of plasma HCY was significantly higher in patients with liver cirrhosis (21.71+/-4.86) micromol/L than that in healthy individuals (8.34+/-3.59) micromol/L. There were three kinds of MTHFR genotypes: +/+ (TT, homozygous mutation), +/- (CT, heterozygous mutation) and -/- (CC, wild type). The frequencies of the three genotypes were as follows: +/+, 29.9%; +/-, 52.9%; -/-, 17.2% in cirrhosis patients and +/+, 19.6%; +/-, 33.9%; -/-, 46.4% in normal subjects. The frequency of homozygous or heterozygous mutation was significantly higher in cirrhosis patients than that in the normal control. Moreover, plasma homocysteine level was markedly higher in patients with MTHFR genetic mutation than those without mutation. CONCLUSIONS: Hyperhomocysteinemia may be an independent risk factor for liver cirrhosis. MTHFR is the main enzyme related to homocysteine metabolism. The genetic mutation of MTHFR C667T is possibly an important mechanism of hyperhomocysteinemia in liver cirrhosis. The level of plasma homocysteine may be an early indicator for liver cirrhosis.