摘要
目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因C677T、胱硫醚合成酶(CBS)基因T27796C、蛋氨酸合成酶(MS)基因A2756G 3种基因突变及血浆同型半胱氨酸(Hcy)水平与脑梗死的关系,进一步确定遗传因素对血浆Hcy水平的影响,以及遗传因素在脑梗死发病中的意义。方法选择年龄与性别基本匹配的脑梗死组62例,健康对照组30名。采用高效液相色谱法测定受检者血浆Hcy水平,并应用多聚酶链反应-限制性内切酶片段长度多态性技术(PCR-RFLP)检测基因表型。计量资料用x±s表示,比较采用t检验和方差分析。基因型和等位基因频率分布采用2χ检验。应用Logistic回归分析筛选脑梗死的危险因素。结果脑梗死组血浆Hcy水平明显高于健康对照组[(23±12)与(11±14)μmol/L,P<0.05],脑梗死组MTHFR基因TT纯合基因型和T等位基因频率(分别为56.5%,71.8%)均明显高于健康对照组(分别为16.7%,35.0%)。MTHFRC677T基因型和等位基因频率分布差异有统计学意义(P<0.05)。MTHFR基因C677T纯合子基因型血浆Hcy水平显著高于野生型[(21±11)与(14±3)μmol/L,P<0.01]。CBS T27796C基因型和等位基因频率分布差异无统计学意义(P>0.05),但CBS基因T27796C纯合子基因型血浆Hcy水平显著高于杂合子基因型[(23±11)与(15±6)μmol/L,P<0.01],又高于野生型[(23±11)与(15±5)μmol/L,P<0.01]。MS A2756G基因型和等位基因频率分布组间差异无统计学意义,血浆Hcy水平组间差异无统计学意义。Logistic回归分析显示脑梗死的危险因素为血浆Hcy水平和MTHFR C677T纯合子基因型。结论血浆Hcy水平与脑梗死的发生有一定联系。MTHFR基因C677T位点纯合子突变、CBS基因T27796C位点纯合子突变可引起血浆Hcy水平升高。MTHFR C677T纯合子突变致血浆Hcy水平增高,可能是引起脑梗死发病的重要遗传因素。
Objective To investigate the relationship of gene mutations of methylenetetrahydro-folate reduc- tase（MTHFR）C677T,cystathionine β-synthase （CBS） T27796C, methionine synthase （MS）A2756G and plasma homocysteine levels in brain infarction. To explore the influence of genetic factors on plasma homocysteine levels and the significance of genetic factors in the development of brain infarction. Methods There were no obvious differences in age and sex between the two groups. The plasma homocysteine levels of 62 brain infarction and 30 healthy controls measured using hyper-performance liquid chromatography with fluorescence detection. Moreover, the polymorphisms of MTHFR genetic C677T, CBS genetic T27796C, MS genetic A2756G were determined by polymerase chain reaction-restriction fragment length polymorphism（PCR-RFI.P） in two groups. Measurement data was expressed with mean±standard deviation ^-x±s. The comparison of measurement data was adopted with T Test and analysis of variance. The distribution of gene type and allele frequencies was adopted with Chi-Square Test. The risk factors for brain infarction were selected with Logistic Regression. Results The plasma homocysteine levels were （23±12）μmol/L in patients with brain infarction, significantly higher than those in healthy controls（11±14）μmol/L （P〈0.05）. The frequencies of MTHFR TT homogenetic type and allele T （56.5%, 71.8%） in brain infarction were significantly higher than that in the healthy controls （16.7%, 35.0%）. There were significant differences in the frequencies of MTHFR mutations between two groups （P〈0.05）. The plasma homocysteine levels in patients with MTHFR TT genotype were markedly higher than those in patients with MTHFR CC genotype/-（21±11）vs（14±3）μmol/L, P〈0. 01]. There were no significant differences in the frequencies of CBS mutations between two groups （P〉0.05）. The plasma homocysteine levels in patients with CBS CC genotype were markedly higher than those in patients with CBS TC genotype [（23 ± 11）vs（15±6） μmol/L, P〈0. 01],and CBS TT genotypeE（23±11）vs（15±5）μmol/L,P〈0.017. There were no significant differences in the frequencies of MS mutations between two groups, and there were no significant differences in plasma Hey levels between AG- genotype and AA genotype of MS. Logistic Regression analysis showed that the plasma homocysteine levels and the genotype of MTHFR C677T were risk factors for brain infarction. Conclusion The plasma homoeysteine levels might be associated with brain infarction. MTHFR TT and CBS CC homogenetic type can raise the plasma homocysteine levels. MTHFR gene C677T mutations may be associated with a predisposition to increase of plasma homocysteine may represent a genetic risk factor for brain infarction.
