The Association Between The C677T Methylenetetrahydro-Folate Reductase Gene Polymorphism And Hyperhomocysteinaemia With Poor Pregnancy Outcomes

Objective: To test the hypothesis that the common missense mutation of 5,10-methylenetetrahydrofolate reductase (MTHFR)(677 C to T,ala to val)and hyperhomocysteinaemia are more prevalent among poor pregnancy outcome women compared with control patients in Han nationality.The correlation of the MTHFR T677/T677 genotypes in mothers and fetuses was also investigated to test for possible maternal-fetal interactions and the possibility of a correlation between serum homocystein and MTHFR genotypes were investigated as well.Methods: The MTHFR genotype was determined for 60 control healthy women and 30 healthy fetuses, 103 poor pregnancy outcome patients (including preeclampsia & eclampsia and unexplained recurrent early fetal loss patients) and the infants of preeclampsia & eclampsia pregnant women by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)method.Results were analyzed with an x2 test for homogeneity.To ensure homogeneity of ethnic background,only samples from Han nationality were analyzed.Serum homocystein was determined by auto fluorescence polarization-immunoassay(FPIA).One way ANOVA and T test were used to compare serum homocystein levels between genotypes and groups,to determine the relationship between serum homocysteinlevels and other factors,also Spearman correlation and odds ratio were used.Results: There was a significant difference in prevalences of the methylenetetrahydrofolate reductase genotypes(T/T,C/Tand C/C) between the preeclampsia & eclampsia group(27.8%,63.0%,and9.2% respectively) and the normal pregnant women group,(P=0.000).Also there was a significant difference in prevalences of the MTHFR genotypes (T/T,C/TandC/C) between the preeclampsia & eclampsia fetuses group(56.0%,18.0%,and26.0% respectively)and the normal fetuses group(P=0.000).There was a significant difference in prevalences of the MTHFR genotypes (T/C,C/T and C/C)between the unexplained recurrent early fetal loss patients group (12.2%,51.0%and 36.8% respectively)and the healthy women group(P=0.016).The frequency of the T677 allele was 59.3% in the preeclampsia & eclampsia group, 65.0% in the preeclampsia & eclampsia fetuses group and 37.8% in the unexplained recurrent early fetal loss patients group. There are significant differences between these groups and the respective control groups (P=0.000-0.010).The serum homocysteine fast levels in the preeclampsia & eclampsia group and unexplained recurrent early fetal loss patients group were both significantly higher than the control groups (P=0.000,0.041). Also there was significant difference between the serum homocysteine level of preeclampsia & eclampsia fetuses and healthy fetuses(P=0.006).The homocysteine fast levels in serum in T/T allele homozygous genotype was higher than that in C/T heterozygous and C/C allele homozygous,there were significant differences between every two genotypes(P=0.000-0.048).The Spearman correlation coefficient between genotypes and homocysteine fast levels is -0.800~-0.844(P=0.000).Conclusion: The results suggest that T/T homozygous genotype and C/T heterozygous of methylenetetrahydrofolate reductase(MTHFR) gene may be an independent risk factor for pregnancy complications.The hyperhomocysteinaemia was also an independent risk factor for poor pregnancy outcomes.So MTHFR mutation is an useful testing, it's screening by molecular biological methods is recommended. Beside this, the test of serum homocystein is also helpful fordetecting the pregnancy complications.