The Relationship Of The Gene Polymorphism Of MTHFR And MTRR With Spontaneous Abortion

Spontaneous abortion is a common clinical disease in gynecological, and its etiology is complex. Now the factors which may cause spontaneous abortion we have found include genetic factors, immunodeficiency, infection factors, endocrine factors, anatomy factors, social factor etc. The incidence of spontaneous abortion is by 10% to 20% in total of pregnancy. Recently the incidence of spontaneous abortion is ascendant. Because of the etiology of spontaneous abortion is not clear, the prevention and treatment of this disease become very difficult for us.Along with the development of molecular biology technology the study on spontaneous abortion genetically factors already has become one of the hot researches, especially for the key enzyme gene polymorphism in folic acid-methionine metabolic circulation. Among them, Methylenetetrahydrofolate reductases (MTHFR) Methyltransferasereductase (MTRR) genetic polymorphism is the point of scholars' study.MTHFR catalyzes the essentially irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyletrahydrofolate.5-methyletrahydrofolate provides one-carbon unit to homocysteine (HCY) which can be methylated into methionine. This effect also can regulate the normal level of HCY in body. Methionine can re-activate into S-adenosylmethionine (SAM) which is che methyl donor in many metabolic reactions in human body. The polymorphism in MTHFR affects the activity and thermal stability of the enzyme, thereby affecting folic acid, methionine metabolism. The polymorphism in MTHFR C677T,A1298C is the hot study. Methionine is the essential amino acid in the process of protein synthesis and metabolism of one carbon unit. Its synthesis is catalyzed by methionine syntheses (MTR coded), and methionine syntheses will loss its activity because of cofactor of vitamin B12 oxidized. Methionine syntheses can regenerate its activity by methyltransferasereductase which encoded by MTRR, through the role of reductive methylation. MTRR mutation plays an important role in folic acid deficiency and abnormal methionine metabolism. The abnormal metabolism of folate and methionine may result in spontaneous abortion.At home and abroad the studies on the relationship between MTHFR, MTRR gene polymorphism and spontaneous abortion have focused on a single or two gene loci. In this article we use the Taqman-MGB probe technology to detect MTHFR C677T, A1298C and MTRR A66G gene polymorphisms at the same time, and analyze the relationship with spontaneous abortion.ObjectiveThe objective is to investigate the relationship of the gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) and methyltransferase reductase (MTRR) with spontaneous abortion.Material and MethodsCollect the oral mucosa cells of spontaneous abortion patients group (60 cases) and control group (100 cases), then extracted DNA from them. MTHFRC677T,A1298C,MTRRA66G genotype are analyzed by a technique of Taqman—MGB. All data were analyzed with spss16.0 software. Differences in the frequencies of alleles and genotypes were analyzed by Pearson'sχ2 test. Differences of measurement data between two groups were compared by independent-samples t test, and all data were indicated as x±s, values were considered as significant at a=0.05. Results(1) There are no significant differences of ages and gestational ages between spontaneous abortion group (28.57±4.80y,10.72±1.21w) and control group (28.41±4.32y,10.68±1.16w).(2) The comprison of the MTHFR C677T polymorphism between spontaneous abortion group and control group:There are significant differences of CC,CT,TT the genotypes of MTHFR C677T between control and cases;The frequency of mutant homozygous genotype CC in spontaneous abortion group is 3.33%, which lower than that in control group (23.00%). The CT genotype frequency (56.67%) is also lower in spontaneous abortion group than that in control group (72.00%) and absolutely; but the TT genotype frequency (40.00%) is higher in spontaneous abortion group. The frequency of CT+TT genotypes in spontaneous abortion group is 96.67%, which also have significant differences with the control group. T allele frequency of spontaneous abortion women is also higher than that of control group (68.33% contrast to 41.00%)。(3) There are significant differences of MTRR AG+GG genotypes between control (41.67%) and cases (11.00%), and the frequency of G allele is 20.83%, which is higher than that of control group (6.00%).(4) The frequency of MTHFRA1298C AC+CC genotypes is 18.33%(spontaneous abortion group),26.00%(control group), there is no significant differences between them. The frequencies of C allele are 9.17%(spontaneous abortion group) and 13.5% (control group), which also have no significant differences between the two group.(5) The frequencies of 677 CT/1298 AC+677 CT/1298 CC+677 TT/1298 AC+677 TT/1298 CC genotypes in cases group are higher than in control group (35.00% contrast to 19.00%).Conclusions(1) The polymerase of MTHFR C677T may be an independent risk factor for spontaneous abortion women. (2) The mutation of MTRR A→G may have relationship with the spontaneous abortions.(3) The mutation of MTHFR 1298 A→C can not induce spontaneous abortion, but when it occurs with the mutation of 677 C→T also can increase the rate of spontaneous abortion.