RFC-1基因多态性与急性脑梗塞的相关性研究

Correlation between Genetic Polymorphism of RFC-1 Gene and Acute Cerebral Infarction

目的 对CRF-1基因多态性与急性脑梗塞的相关性进行初步研究,旨在为急性脑梗塞的临床预防提高一定的科学数据和临床参考.方法 随机抽取100例急性脑梗塞患者为ACI组,同期与ACI组患者年龄、性别以及生活习惯大致相同的健康体检者50人为对照组,留取5 ml空腹静脉血进行RFC-1的基因及血浆半胱氨酸检测.结果 ① ACI组中血浆Hcy水平较健康对照组显著性升高,其差异有统计学意义（P〈0.05）.根据对照组血浆Hcy水平的四分位数进行分级,结果显示随着血浆Hcy水平的升高,急性脑梗塞的危险逐渐增加,并呈现出一定的剂量效应关系.② 经Hardy-Weinberg平衡检验发现,RFC-1基因位点在两组中均无统计学意义（χ^2=4.4288、0.11;P=0.6877、0.71）.③ 两组RFC-1基因及等位基因频率比较,在ACI组中3种基因的频率依次为25 %、39 %及36 %,健康对照组依次为：40 %、42 %及18 %,两者相比具有统计学差异.等位基因频率的比较中也发现G出现显著高于A,具有统计学差异.④ 在RFC-1基因多态性与急性脑梗塞之间的关系分析中发现,携带GG基因型的者较携带AA型基因者患急性脑梗塞的风险显著升高（OR=2.95,95 % CI：1.25～6.05）;而AG基因型对急性脑梗塞患者无影响.为了进一步分析,我们将AA和AG基因型者合并分析,结果发现携带GG基因者患急性脑梗塞的风险仍然升高2.15倍,但对急性脑梗塞患病危险无显著性差异.⑤ 血浆Hcy与RFC-1基因的交互作用和急性脑梗塞易感性的分析中发现,与Hcy正常且携带A等位基因者相比,RFC-1纯合突变者患有急性脑梗塞的危险升高3.69倍,单独高Hcy血症患者危险升高2.98倍,正常Hcy水平但携带GG型基因者风险升高3.17倍.在Logisitic回归模型中,Hcy与RFC-1的交互作用不明显.结论 ① RFC-1基因的80号位点A→G的突变可能对血浆同型半胱氨酸浓度产生影响.② RFC-1基因多态性与急性脑梗塞的易感性,改基因的纯合子突变大大增加了本病发生的风险.

Objective To preliminarily examine the correlation between RFC-1 gene polymorphism and acute cerebral infarction （ACI） in an attempt to provide scientific data for the prevention of ACI.Methods After fasting,the venous blood （5 ml） was harvested from 100 ACI patients and 50 healthy people who were matched to the patients in terms of age,gender and living habits.RFC-1 gene polymorphism and plasma Hcy levels were detected.Results ① The levels of plasma Hcy were significantly higher in ACI group than in healthy control group,and the difference was statistically significant （P〈0.05）.According to the quartiles of plasma Hcy levels in the control group,the Results revealed that with the increase of the plasma Hcy levels,the risk of ACI was greatly increased,showing a certain dose-effect relationship.② Hardy-Weinberg equilibrium test showed that RFC-1 gene locus was not statistically different between the two groups （χ^2=0.6103,0.3402;P=0.74,0.84）.③ Comparison of the frequency of RFC-1 gene and allele showed that in group ACI,the frequencies of the three types of genes were 25 %,39 % and 36 %,while they were 40 %,42 % and 18% in control group.There was a statistically significant difference between the two groups.It was also found that the frequency of G was significantly higher than that of A （P〈0.05）.④ People carrying GG gene were more likely to develop ACI than those carrying AA gene （OR=2.95,95 % CI：1.25-6.05）.AG gene had no effects on ACI patients.Additionally,we combined the subjects with AA gene and AG gene for further analysis.The Results also showed that the risk of ACI was increased by 2.15 times in people carrying GG gene.⑤ The risk of ACI was increased by 3.69 times in people with RFC-1 homozygous nonsense mutation when compared with those with normal Hcy levels and allele gene A.The risk of ACI was increased by 2.98 times in people with only high plasma Hcy levels,and it was 3.17 times higher in people with normal Hcy levels and GG gene.In the Logistic regression model,the interaction between Hcy and RFC-1 was not obvious.Conclusion ① The mutations of RFC-1 gene in No.80 locus A→G may have an effect on the concentration of plasma homocysteine.② RFC-1 gene polymorphism and the susceptibility of ACI,as well as the homozygous nonsense mutation of gene can greatly increase the risk of ACI.