Individualized Folic Acid Supplementation based on Polymorphisms of Methylenetetrahydrofolate Reductase (MTHFR) and Methionine Synthase Reductase (MTRR), Compared with Traditional Folic Acid Supplementation, Reduces Gestational Diabetes Mellitus

Abstract Backgroud: Folic Acid (FA) may contribute to the development of gestational diabetes mellitus (GDM), but existing studies are inconsistent. We examined the genotype distributions and allele frequencies of methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C and methionine synthase reductase (MTRR) A66G polymorphisms of pregnant women in China, and compared the effects of individualized folate supplementation and traditional FA supplementation on GDM.Methods: The genotype distributions and allele frequencies of MTHFR C677T, A1298C and MTRR A66G polymorphisms in 968 pregnant women (case group) were tested. FA metabolism was ranked at four levels, and then pregnant women of different levels are supplemented with different doses of FA at different periods. The case group was followed up for pregnancy complications and compared with 1,940 pregnant women traditionally supplemented with FA in the same hospital (control group).Results: The allele frequencies of MTHFR C677T were 63.3% (C) and 36.7% (T), those of MTHFR A1298C were 79.3% (A) and 20.7% (C), and those of MTRR A66G were 75.0% (A) and 25.0% (G). Compared with control group, the incidence of GDM in the case group were significantly lower, especially in high-risk pregnant women after FA supplementation.Conclusion: Traditional FA supplementation based on personal habits is controversial, but the use of polymorphisms of genes to clarify the FA metabolism of pregnant women, appropriate, timely and accurate supplementation of FA can effectively reduce gestational diabetes, especially for high-risk pregnant women.

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Association between Maternal and Fetal MTHFR C677T and MTRR A66G Polymorphisms with the Risk of NTDs: A Systematic Review and Meta-Analysis Study

10.32592/ircmj.2021.23.11.1350 ◽

2021 ◽

Keyword(s):

Folic Acid ◽

Subgroup Analysis ◽

Methylenetetrahydrofolate Reductase ◽

Meta Analysis ◽

Mthfr C677t ◽

C677t Polymorphism ◽

Mthfr C677t Polymorphism ◽

Analysis Study ◽

Methionine Synthase Reductase ◽

Mtrr A66g

Background: Neural tube defects (NTDs) are classed as multifactorial birth defects of the brain and spinal cord that arise during embryonic development. Although the etiology is not well understood, NTDs are reported to be prevented by maternal folic acid supplementation before and during early pregnancy. This meta-analysis study aimed to assess the association between fetal and maternal methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms with the risk of NTDs. Methods: The PubMed, Scopus, and Springer Link databases were searched (from March 2000 to November 2020) for the literature on the association between MTHFR C677T and MTRR A66G polymorphisms with the risk of NTDs. Results: In total, 33 studies were reviewed in the present study, and it was revealed that, unlike MTRR A66G polymorphism, MTHFR C677T was statistically associated with the risk of NTDs in the overall population. The results of subgroup analysis showed that the Indian subcontinent subgroup with maternal MTHFR C677T polymorphism and the European subgroup with fetal MTHFR C677T polymorphism was significantly susceptible to NTDs. Conclusion: The obtained results revealed that, unlike MTRR A66G, maternal and fetal MTHFR C677T polymorphism was significantly associated with NTDs. Subgroup analysis also demonstrated that folic acid deprivation can be considered the main cause of MTHFR C677T polymorphism in some areas.

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Interaction between Polymorphisms MTHFR C677T and MTRR A66G and Vitamin Levels in Pregnant Women.

Blood ◽

10.1182/blood.v104.11.3687.3687 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3687-3687

Author(s):

Elvira M. Guerra-Shinohara ◽

Patricia R. Barbosa ◽

Luiz F. Sampaio-Neto ◽

Rosario D. Hirata ◽

Mario H. Hirata ◽

...

Keyword(s):

High Risk ◽

Pregnant Women ◽

Mthfr C677t ◽

Serum Levels ◽

Serum Folate ◽

P Value ◽

Methionine Synthase Reductase ◽

Mtrr A66g ◽

Increased Risk ◽

677T Allele

Abstract In the homocysteine metabolic pathway, several key enzymes, including methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR), have been implicated in abnormal homocysteine accumulation in the presence of rare alleles. In previous study, we showed that lower maternal Cbl levels were associated with higher tHcy and lower S-adenosylmethionine/S-adenosylhomocysteine ratio in pregnant women and their neonates.The aim of this study is to investigate whether MTHFR and MTRR polymorphisms are involved in the risk for elevated total homocysteine (tHcy) and its interaction with low cobalamin (Cbl) or serum folate (SF) levels. Genotypes for polymorphisms MTHFR C677T and MTRR A66G were determined by PCR-FLRP. The serum levels of Cbl, SF and tHcy were determined in 377 pregnant women (37–42 weeks of gestational age), and cutoff values for Cbl and SF were considered the first quartile (low values). Four models of univariate logistic regression analyses were used (Table 1). Pregnant women with MTHFR 677T allele have high risk for elevated tHcy that is increased when 677T allele is associated with low Cbl. Increased risk for elevated tHcy is also met when MTRR 66G allele and low Cbl levels were associated. Women with low SF and common MTHFR and MTRR alleles have high risk for elevated tHcy, that is increased when in association with 677T allele or with 66G allele. Interaction between MTHFR C677T and MTRR A66G polymorphisms and vitamins levels in pregnant women Dependent variables Comparation levels (N) P value Odd Ratios 95% CI P for trend: (a) P<0.001; (b) P<0.001; (c) P=0.067; (d) P<0.001 tHcy>8.3μmol/L MTHFR 677CC genotype and Cbl> 115.8 pmol/L (ref) (136) a 1.00 MTHFR 677CC genotype and≤Cbl 115.8 pmol/L (45) 0.298 1.57 0.67 – 3.63 MTHFR 677CT and 677TT genotypes and Cbl>115.8 pmol/L (145) 0.015 2.09 1.16 – 3.77 MTHFR 677CT and 677TT genotypes and≤Cbl 115.8 pmol/L (48) 0.001 4.63 2.22 – 9.65 tHcy>8.3μmol/L MTHFR 677CC genotype and SF > 10.9 nmol/L (ref) (148) b 1.00 MTHFR 677CC genotype and≤SF 10.9 nmol/L (33) 0.008 3.20 1.35 – 7.59 MTHFR 677CT and 677TT genotypes and SF > 10.9 nmol/L (133) 0.035 1.95 1.05 – 3.61 MTHFR 677CT and 677TT genotypes and≤SF 10.9 nmol/L (59) 0.001 6.62 3.31 – 13.26 tHcy>8.3μmol/L MTRR 66AA genotype and Cbl> 115.8 pmol/L (ref) (96) c 1.00 MTRR 66AA genotype and ≤Cbl 115.8 pmol/L (23) 0.222 1.90 0.68 – 5.29 MTRR 66AG and 66GG genotypes and Cbl>115.8 pmol/L (183) 0.418 1.29 0.70 – 2.39 MTRR 66AG and 66GG genotypes and ≤Cbl 115.8 pmol/L (69) 0.013 2.46 1.21 – 5.01 tHcy>8.3μmol/L MTRR 66AA genotype and SF > 10.9 nmol/L (ref) (92) d 1.00 MTRR 66AA genotype and ≤SF 10.9 nmol/L (27) 0.006 3.83 1.47 – 9.96 MTRR 66AG and 66GG genotypes and SF > 10.9 nmol/L (186) 0.399 1.34 0.68 – 2.63 MTRR 66AG and 66GG genotypes and≤SF 10.9 nmol/L (65) 0.001 4.78 2.26 – 10.10 In conclusion, the interaction between MTHFR and MTRR polymorphisms and low folate and cobalamin serum levels may explain the increased risk for elevated tHcy found in pregnant women.

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Folic acid deficiency related to hyperhomocystinemia has less correlation with Gestational Diabetes Mellitus (GDM)

Update Dental College Journal ◽

10.3329/updcj.v6i1.29213 ◽

2016 ◽

Vol 6 (1) ◽

pp. 1-7

Author(s):

Shamim Ara Begum ◽

Ibrahim Khalil ◽

Chanchal Kumar Mandal ◽

Md Moynul Hasan ◽

Mohammad Ali Kawsar

Keyword(s):

Diabetes Mellitus ◽

Folic Acid ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Metabolic Enzyme ◽

Control Group ◽

Case Group ◽

Folic Acid Deficiency ◽

Acid Deficiency ◽

The Mean

Gestational diabetes mellitus (GDM) is a different degree of the glucose intolerance that begins during pregnancy. GDM affects maternal and child health and is associated with a potential for preeclampsia, caesarean delivery due to macrosomic baby and type 2 diabetes in the mother, and with higher rates of perinatal mortally and many abnormalities in the infant. Homocysteine is a naturally occurring amino acid. Hyperhomocysteinemia(Hcy) is increased homocysteine levels which are associated folic acid deficiency. Hcy is regulated by several factors including genetically determined metabolic enzyme alteration, nutritional status, underlying disease, certain medication, age and pregnancy. A total of (40 case+40control) 80 patients are included in this study, it was observed that majority 21(52.5%) patients were age belonged to 31-35 years in case group and 17(42.5%) patients were age belonged to 31-35 years in control group. The mean age was found 30.5±4.2 years in case group and 29.05±4.2 years in control group. Majority 19(47.5%) patients had 3rd gravida in case group and 20(50.0%) patients had 3rd gravida in control group. Majority patients BMI belonged to 25-29.9 kg/m2 (over weight) in both groups which was 21(52.5%) in case and 32(80.0%) in control group. The mean BMI was found 28.9±3.4 kg/m2 in case and 28.53±2.9 kg/m2 in control group. The difference was not statistically significant (p>0.05) between two groups. Studies have shown that folate deficiency is associated with increased homocysteine levels in blood.Update Dent. Coll. j: 2016; 6 (1): 01-07

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Prevalence of the MTHFR C677T Mutation in Fertile and Infertile Women

Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics ◽

10.1055/s-0037-1606289 ◽

2017 ◽

Vol 39 (12) ◽

pp. 659-662 ◽

Cited By ~ 3

Author(s):

Adriana Soligo ◽

Ricardo Barini ◽

Joyce Annichino-Bizzacchi

Keyword(s):

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

Mthfr Gene ◽

Control Group ◽

Case Group ◽

Infertile Women ◽

Chi Squared ◽

History Of ◽

C677t Mutation ◽

Fertile Women

Introduction The importance of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in infertile women remains controversial. Objective To evaluate if the MTHFR C677T mutations are more frequent in infertile women, and if they can be associated with the occurrence of infertility in the Brazilian population. Methods This case-control study included 130 infertile women consulting at a private clinic between March 2003 and March 2005 (data previously published), and 260 fertile women attending the family planning outpatient clinic of our institution between April 2012 and March 2013. Data analysis The Chi-squared and Fisher Exact tests were used to evaluate the association between the presence of the MTHFR C677T mutation and a history of infertility. Results The frequency of the mutation was of 58.5% for the case group (n = 76) and of 49.2% for the fertile controls (n = 128). The mutation was homozygous in 13 women in the case group (10%) and in 23 of the fertile women in the control group (8.8%). These differences were not statistically significant. Conclusions These results suggest that the presence of the MTHFR C677T mutation does not constitute a risk factor for infertility, even when the mutation is homozygous. Further studies are needed to confirm whether research on this mutation should be considered unnecessary in women with infertility.

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The Effect of Myo-inositol Supplementation on the Prevention of Gestational Diabetes in Overweight Pregnant Women: a Randomized, Double-blind, Controlled Trial

10.21203/rs.3.rs-260476/v1 ◽

2021 ◽

Author(s):

Sedighe Esmaeilzadeh ◽

Reza Ghadimi ◽

Sepideh Mashayekhamiri ◽

Mouloud Agajani Delavar ◽

Zahra Basirat

Keyword(s):

Folic Acid ◽

Gestational Diabetes ◽

Insulin Therapy ◽

Pregnant Women ◽

Controlled Trial ◽

Daily Intake ◽

Control Group ◽

Oral Glucose ◽

Number Needed To Treat ◽

Double Blind

Abstract Purpose: This study is striving to test the hypothesis that a low dosage of myo-inositol supplementation may decrease the likelihood of gestational diabetes in overweight, pregnant women. Methods: A randomized, double-blind, controlled trial was performed on 60 eligible overweight, pregnant women at 12-14 weeks of gestation at two Iranian obstetric clinics. The participants were divided into two groups based on blocked randomization. The myo-inositol group, receiving 2000 mg plus 200 μg folic acid daily and the control group, receiving 400 μg of folic acid daily from 14 - 24 gestational weeks. The occurrence of gestational diabetes was determined based on 75-g 2-hour oral glucose tolerance test (OGTT) at 24–28 gestational weeks, which was the primary outcome of the study. The secondary outcomes were: the evaluation of insulin therapy, insulin resistance, and lipid profile, gestational weight gain, as well as fetal and maternal outcomes. Results: The incidence of gestational diabetes in myo-inositol group was noticeably minimized compared with that of the control group (RR 0.29, 95% CI 0.09-0.94, p= 0.037). There were no differences between the two groups in terms of fasting blood sugar, fasting insulin, HOMA-IR, insulin therapy, and triglyceride. There was no report of severe adverse drug reactions, either.Conclusions: The absolute risk reduction and the ‘‘Number-Needed-to-Treat’’ for gestational diabetes were 26.8% (95% CI, 5.6–48) and 3.7 (95% CI, 2.1–18.0), respectively. Hence, it can be concluded that approximately one out of every four overweight pregnant women receiving myo-inositol benefitted from its daily intake.

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Serum Zinc and Copper Levels in Gestational Diabetes Mellitus in a Tertiary Care Hospital of Bangladesh

BIRDEM Medical Journal ◽

10.3329/birdem.v8i1.35040 ◽

2017 ◽

Vol 8 (1) ◽

pp. 52-55 ◽

Cited By ~ 1

Author(s):

Farzana Akonjee Mishu ◽

MA Muttalib ◽

Bilkis Sultana

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Pregnant Women ◽

Serum Zinc ◽

Control Group ◽

Case Group ◽

Third Trimester ◽

Group I ◽

Significant Difference

Background: The term gestational diabetes mellitus (GDM) is becoming a major health problem in developing countries undergoing rapid changes in lifestyle, dietary habits and body mass index. GDM is associated with an increased incidence of congenital abnormalities which is also aggravated by mother’s zinc and copper deficiency. Zinc and copper are essential trace elements for normal embryogenesis and fetal growth and their deficiency increase mortality and morbidity of mothers, embryos and neonates. This study was designed to evaluate the association of serum zinc and copper with GDM in second and third trimester.Methods: It was a case-control study. This study was conducted in Mymensingh Medical College Hospital during the period from July 2013 to June 2014 to evaluate the association of zinc and copper levels of pregnant women with GDM. A total induded of 172 subjects were participated in this study; among them 86 women diagnosed with GDM were selected as case (Group-I) and 86 healthy pregnant women were control (Group- II).The case group was again subdivided as Group Ia and Ib according to second and third trimester respectively. Control group was also subdivided as Group IIa and IIb according to second and third trimester respectively. Student’s unpaired ‘t’ test was used to analyse the data between groups. For analytical purpose 95% confidence limit (p<0.05) was taken as level of significance.Results: There was significant difference in serum zinc and copper levels in cases compared to control group. Highly significant difference (p<0.001) was found when serum zinc was compared between women with GDM and normoglycemic pregnant women in second and third trimester. Serum copper level was significantly increased in cases compared to control group in second trimester and the difference was found highly significant (p<0.001) and significant difference (p<0.01) was found in GDM compared to normoglycemic pregnant women in third trimester.Birdem Med J 2018; 8(1): 52-55

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Anemia ibu hamil pada perokok pasif Di wilayah puskesmas kota banjarmasin tahun 2016

Jurnal Skala Kesehatan ◽

10.31964/jsk.v10i1.206 ◽

2019 ◽

Vol 10 (1) ◽

pp. 1-10

Author(s):

Hapisah Hapisah ◽

Tri Tunggal

Keyword(s):

Folic Acid ◽

Pregnant Woman ◽

Pregnant Women ◽

Health Center ◽

Cigarette Smoke ◽

Control Group ◽

Case Group ◽

Pregnancy And Childbirth ◽

Anaemia In Pregnancy ◽

In Pregnancy

Anaemia in pregnancy increases the risk of complications in pregnancy and childbirth, e.i. maternal death, prematurity, LBW, and perinatal mortality. Many factors cause anaemia, including when pregnant woman got exposure from tar, free radicals and carbonmonoxide contained in cigarette smoke that is inhaled directly by unintentionally. CO is directly bound in maternal hemoglobin so the ability of hemoglobin to be much greater binds CO than oxygen. Inhaling tobacco smoke in passive smoking, has far lower levels of folic acid, exposure to acid smoking causes a disruption of iron metabolism in red bloodcells. Iron very useful in the formation of hemoglobin, deficiencies of folic acid and iron can cause defects in the fetus and anaemia. Research purpose to know the incidence of anaemia in pregnant women passive smokers in Banjarmasin City Health Center 2016. Research method uses a case control study design. Population is all pregnant women in Banjarmasin City Health Center 2016. Samples were 120 people, composed of 60 cases pregnant women anaemia, and control were 60 pregnant women anaemia which doesn’t meet the criteria of inclusion and exclusion. Results showed 36 pregnant women were exposed to cigarette smoke, 24 respondents (40%) had a case group and 12 respondents (20%) in control group. There is a meaningful relationship between pregnant women passive smokers with incidence of anemia, value of p = 0.028 0.05 and OR α < 2.67 (CI-6.034 1.178). Exposure to cigarette smoke are at risk of 2.67 times against the incidence of anaemia pregnant woman than not exposed. Keywords: passive smokers, anemia in pregnancy

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Association of MTRR A66G polymorphism (but not of MTHFR C677T and A1298C, MTR A2756G, TCN C776G) with homocysteine and coronary artery disease in the French population

Thrombosis and Haemostasis ◽

10.1160/th05-04-0262 ◽

2005 ◽

Vol 94 (09) ◽

pp. 510-515 ◽

Cited By ~ 31

Author(s):

Yves Juilliére ◽

Mirande Candito ◽

Charles E. Adjalla ◽

Pierre Gibelin ◽

Bernard Herbeth ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

Methionine Synthase ◽

French Population ◽

Methionine Synthase Reductase ◽

Mtrr A66g ◽

Artery Disease ◽

The Individual

Summarymethylenetetrahydrofolate reductase polymorphism (MTHFR C677T) is an established determinant of homocysteine plasma level (t-Hcys) while its association with coronary artery disease (CAD) seems to be more limited. In contrast, the association of the substitutions A2756G of methionine synthase (MTR), A66G of methionine synthase reductase (MTRR) and C776G of transcobalamin (TCN) to both t-Hcys and CAD needs to be evaluated further. The objective was to evaluate the association of these polymorphisms with t-Hcys and CAD in a French population. We investigated the individual and combined effects of these polymorphisms and of vitamin B12 and folates with t-Hcys in 530 CAD patients and 248 matched healthy controls. t-Hcys was higher in the CAD group than in controls (11.8 vs 10.4 μM, P<0.0001) and in carriers of MTRR AA and MTHFR 677TT than in those carrying the most frequent allele of both polymorphisms (13.8 vs 11.4 μM, P=0.0102 and 12.5 vs 11.0 mM, P=0.0065 respectively). The frequency of MTRR A allele was higher in CAD patients than in controls (0.48 [95% CI: 0.44-0.52] vs 0.38 [95% CI: 0.32-0.44], P=0.0081) while no difference was observed for MTHFR 677T frequency. In multivariate analysis, t-Hcys > median and MTRR AA genotype were two significant independent predictors of CAD with respective odds ratios of 3.1 (95 % CI: 1.8-5.1, P<0.0001) and 4.5 (95% CI: 1.5-13.1, P=0.0051). In conclusion, in contrast to North Europe studies, MTRR AA genotype is a genetic determinant of moderate hyperhomocysteinemia associated with CAD in a French population without vitamin fortification.

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Significant Interaction of MTHFR C677T, A1298C and MTRR A66G Polymorphisms on the Risk of Low Birth Weight Infants

10.21203/rs.3.rs-650493/v1 ◽

2021 ◽

Author(s):

Shuang Sun ◽

Ying Liu ◽

Xuehua guo ◽

Xun Zhao

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

Gene Interaction ◽

Mthfr Gene ◽

Taqman Probe ◽

Low Birth Weight Infants ◽

Methionine Synthase Reductase ◽

Mtrr A66g

Abstract Background: To explore the relationship between maternal methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C, Methionine Synthase Reductase (MTRR) gene A66G and the recurrence of low birth weight(LBW) in offspring. Methods: Allele-specific polymerase chain reaction (ASPCR) assay combined with TaqMan probe technique were used to detect the mother’s MTHFR and MTRR genotypes respectively. And unconditional logistic regression analysis was used to evaluate the associations of MTHFR and MTRR polymorphisms, and gene-gene interaction with low birth weight.Results: MTHFR 677TT and 1298CC were independently associated with a higher risk of LBW (OR:2.22, 95%CI:1.14-4.34 and OR:2.82, 95% CI:1.15-6.87,respectively). The MTRR A66G polymorphism was associated with an significant association of LBW when combined with the MTHFR 677TT genotype, although there was no association found between LBW and MTRR A66G alone.Moreover, two or more risk genotypes carriers showed higher odds of LBW than null risk genotype one.Conclusion: Maternal MTHFR gene 677TT, 1298CC can increase the risk of LBW in the offspring.The MTRR A66G polymorphism was not associated with LBW alone. But it may exacerbate the effect of the MTHFR C677T variant.

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Thyroid Dysfunction in Pregnant Women with Gestational Diabetes Mellitus

Current Diabetes Reviews ◽

10.2174/1573399816666191223111833 ◽

2020 ◽

Vol 16 (8) ◽

pp. 895-899 ◽

Cited By ~ 1

Author(s):

Shahin Safian ◽

Farzaneh Esna-Ashari ◽

Shiva Borzouei

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Pregnant Women ◽

Thyroid Dysfunction ◽

Control Group ◽

Thyroid Peroxidase ◽

Free T4 ◽

Significant Difference ◽

Experimental Group

Aims: Investigation thyroid dysfunction and autoimmunity in pregnant women with gestational diabetes mellitus. Background: This article was written to evaluate the thyroid function and anti-thyroid peroxidase (anti- TPO) antibodies in pregnant women with gestational diabetes mellitus (GDM). Method: A total of 252 women with GDM and 252 healthy pregnant women were enrolled. Thyroid tests, including TSH, FreeT3, Free T4, and anti-TPO were performed for all women at 24–28 weeks of gestation. Data analysis was then carried out using SPSS ver. 22. Result: There was a significant difference between the experimental group (38.4%) and the control group (14.06%) in terms of the prevalence of subclinical hypothyroidism (p= 0.016). The frequency of anti-TPO was higher in the experimental group than the control group and positive anti-TPO was observed in 18.6% of women with GDM and 10.3% of healthy pregnant women (P= 0.008). Conclusion: Thyroid disorders are observed in pregnant women with GDM more frequently than healthy individuals and it may be thus reasonable to perform thyroid tests routinely.

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