The Gene Polymorphism Of MTHFR And Homocysteine Metabolism Abnormality Associated With Pre-clampsia

Objective: To study the significance of C677T and A1298C mutation of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene in patients with pre-clampsia. To study on the changes and clinical significance of serum homocysteine(Hcy),folic acid(FA)and Vitamin B₁₂ levels in pregnant women. We will explore etiopathology of pre-clampsia in the molecular genetics mechanism and the possible correlation between nourishment, bite and sup with pre-clampsia.Methods: In our study,50 patients with pre-clampsia and 40 normal controls, matched for age and week of gestation, were recruited. DNA was extracted from peripheral blood.â‘ The mutation of the 677C→T and 1298A→C transition of MTHFR was invetigated by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)method. The products of enzyme digestion were separated by electrophoresis in 8%agarose gel, dyed with EB and analysed by gel aerial image.â‘¡Hcy concentration was determined by fluorescence polarization immunoassay(FPIA).And serum folic acid and vitamin B₁₂ levels were detected with microparticle enzyme immunoassay(MEIA).â‘¢All data were analysed with spss10.0 software. Two group comparing uses t test, and all data figure with x±s. Percentage comparing usesχ2 test. P<0.05 is used as the marked differentia.Results:â‘ The genotype frequencies of MTHFR 677C→T were 14.0% for TT,42.0% for TC and 44.0% for CC in the pre-clampsia group, respectively, while 7.5% for TT,20.0% for TC and 72.5% for CC in the control group. There were significant difference in frequencies of TT and TC genotype between the two groups(P <0.05).In the patients with pregnancy induced hypertension,the total mutant T allele frequency of MTHFR gene was significantly higher than that in control group(P <0.05).â‘¡The genotype frequencies of MTHFR A1298C were 58.0% for AA,36.0% for AC and 6.0% for CC in the pre-clampsia group, respectively, while 60.0% for AA,35.0% for AC and 5.0% for CC in the control group. There was no significant difference in the frequencies of genotype and alleles between the two groups(P>0.05,P>0.05).â‘¢The mean level of plasma Hcy in the pre-clampsia group was 12.00±4.59μmol/ L,in control group was 7.85±1.51μmol/L.It was higher in pre-clampsia group than that in control group(P <0.01).The levels of Hcy in the severe Hypertensive disorder complicating Pregnancy group were higher than those in the normal pregnant group(P <0.01).There was no significant difference in the levels of Hcy between the normal pregnant group and the mild pre-clampsia group( P>0.05).â‘£The mean level of plasma folate was lower in the pre-clampsia group 7.90±1.70nmol/ L,than that in the control group (15.32±2.86 nmol/ L)(P<0.001). There was no significant difference in the mean level of vitamin B₁₂ between the two groups(P>0.05).⑤There was a negative correlation between the plama concentration of folate and Hcy in each group(r=-0.550,P <0.001;r=-0.582,P <0.05).There was a negative correlation between the plasma concentration of vitamin B₁₂ and Hcy in each group(r=-0.315,P <0.05;r=-0.287,P <0.05)。Conclusions:1.The genetic polymorphism of MTHFR C677T is associated with the development of pre-clampsia.2.The point mutation of A1298C of MTHFR may have no relationship with pre-clampsia.3.Hyperhomocysteinemia is a risk factor of pathogenesis and development of pre-clampsia.4.Serum Hcy was negatively correlated with FA and vitamin B₁₂ level in normal pregnant group and pregnant induced hypertension group.The lack of folate in pregnancy can induce the high level of Hcy in plasma,which may be related to the occurrence of pre-clampsia.