The Correlation Between MTHFR, Fibrinogen Gene Polymorphism And Cerebral Infarction

Objective: We have developed a SNP detection system earlier. The purpose of the study was to evaluate the platform for detecting methylenetetrahydrofolate reductase(MTHFR) 677C/T and Fibrinogen(Fbg)β-455G/A, -148C/T and 448G/A gene polymorphism accuracy and dependability. Methods: The DNA of 99 cerebral infarction cases and 103 normal cases was amplified using PCR. When Probes were designed, the SNP information in GenBank was utilized. After coupling with florescent microspheres, probes were hybridized with fragments of interest. Then the SNPs were analyzed on liquid gene chips platform. Results: (1) Samples were regarded as wild type, heterozygous and homozygous, if the allele mutation rates were 0~0.25, 0.40~0.70 and 0.80~1 respectively. (2)The accuracy of using these cut-off values were 99.2%, using DNA sequencing as the golden standard. (3)The coefficient of variation of the technique was between 2.5%~18.5%. Conclusions: Liquid gene chips can detect MIHFR 677C/T and Fbgβ-455G/A,-148C/T and 448G/A SNP with high accuracy and reliability. It has the potential of being used in clinical settings on a large scale. Objective: The purpose of the study was to evaluate the correlation between MTHFR677C/T and Fbgβ448G/A polymorphism and cerebral infarction. The correlation among MTHFR677C/T polymorphism, cerebral infarction and hyperhomocysteinemia is also evaluated. Methods: We conducted a case control study on 193 subjects and all cases were reported using case report forms (CRF). The MTHFR677C/T and Fbgβ448G/A polymorphism was detected using liquid gene chips in 90 stroke patients and 103 normal controls and the homocysteine levels were determined with high performance liquid chromatography in 90 cases of cerebral infarction and 50 normal controls. Results: No obvious differences were observed in Fbg448A allele and GG, GA, AA frequency between stroke cases and normal controls (p=0.706). Even though higher frequency of T allele and CT, TT genotype was observed in cerebral infarction cases than that in normal cases, there were no statistically significant differences between these two groups. An average of 14.47±10.19umol/L homocysteine was observed in stroke patients, which was much higher than that in normal group (p=0.030). Logistic analysis revealed that the odds ratio (OR) was 1.842 with 95% confidence interval (CI) from 1.129 to 3.004, excluding age, gender, drinking and smoking status. After stratification of subjects according to gender, homocysteine levels were only significantly different in the female subgroup (p=0.039); male subgroup showed no obvious difference in homocysteine levels (p=0.171). Homocysteine levels much higher in patients with MTHFR677TT genotype than those with CC and CT genotype (P<0.05). Conclusions: There is no correlation between Fbg448G/A, MTHFR677C/T polymorphism and cerebral infarction. Hyperhomocysteinemia is a risk factor for cerebral infarction, especially for females. MTHFR677TT genotype may contribute to hyperhomocysteinemia.