Serum Folate, MTHFR C677T Polymorphism and Esophageal Squamous Cell Carcinoma Risk

This study examined associations between MTHFR C677T polymorphism and serum folate concentrations with the risk of esophageal precancerous lesions （EPL） and esophageal squamous cell carcinoma （ESCC）. The highest quartile of serum folate concentration significantly decreased the risk of ESCC compared with the lowest quartile （0R=0.11; 95% CI, 0.04-0.33; P〈0.05）. MTHFR 677 C〉T polymorphism was associated with the risk of ESCC by using chi-square tests （P〈0.05）. For the CT genotype, the risk of ESCC significantly increased in study participants with low serum folate concentrations （〈26.92μg/L） compared with participants with high serum folate concentrations （〉26.92 μg/L） by using multinomial logistic regression models. The MTHFR genotype may further modify associations between serum folate concentrations and the risk of ESCC, but it was not significantly associated with the risk of EPL.

Association of Bone Turnover Levels with MTHFR Gene Polymorphisms among Pregnant Women in Wuhan, China

Pregnancy is a critical stimulator of bone mineral resorption. We used to find the MTHFR gene polymorphisms are related with blood lead levels among pregnant women. Pregnancy-stimulated bone turnover may be associated with MTHFR gene polymorphisms too. In this article, we aimed to determine the relationship between MTHFR gene polymorphisms and bone turnover rates among the pregnant women. The participants including pregnant and non-pregnant women were selected and recruited during their routine prenatal or physical examination from July to October in 2012. A total of 1000 participants, including 250 pregnant women in the first, second, and third trimesters and 250 non-pregnant women, were enrolled in the study. Finally, after excluding 27 participants unable to provide blood samples, 973 eligible participants （i.e., 234, 249, and 248 pregnant women in the first, second, and third trimesters, respectively, and 242 non-pregnant women） were included in the research. The MTHFR gene 1298CC homozygote carriers were more susceptible to yield higher plasma homocysteine levels than the 1298AA/AC carriers, with standardized coefficients of 0.086 （P〈0.05） and 0.104 （P〈0.01） of all the participants and the pregnant women, respectively. The MTHFR gene 1793AA homozygote carriers more likely showed higher plasma osteocalcin levels （standardized β=0.091, P〈0.01） than the 1793GG/GA carriers among all the subjects. Plasma homocysteine levels were positively correlated with blood lead levels among the participants and the pregnant women with standardized coefficients of 0.320 （P〈0.01） and 0.179 （P〈0.01）, respectively. Plasma osteocalcin levels were positively associated with blood lead levels among pregnant and non-pregnant women with standardized coefficients of 0.084 （P〈0.05） and 0.125 （P〈0.01）, respectively. In conclusion, homocysteine and osteocalcin contents in plasma are associated with the MTHFR gene A1298C polymorphism and blood lead levels among pregnant women. The MTHFR gene A1298C polymorphism-related homocysteine is a possible risk factor for increased blood lead levels among Chinese women.

Methylene Tetra-Hydrofolate Reductase Gene Polymorphism and Endometrial Perfusion in Unexplained Female Infertility

Aim of the study: Examing the role of Methylene tetra-hydrofolate reductase (MTHFR C677T) polymorphisms in unexplained female infertility. Methods: The study was conducted on women with unexplained infertility attending the Infertility Clinic at El-Shatby University Hospital, Alexandria, during the period from October 2020 to October 2021. Uterine artery Doppler assessment and detection of MTHFR C677T gene mutation were done. The frequencies of homozygous and heterozygous gene mutations were determined. Results: In group I, 35 cases had abnormal uterine artery Doppler compared to 22 normal cases in group II. As regards MTHFR C677T gene mutation, 19 cases were positive in group I (7 were homozygous and 12 were heterozygous) and only one case was positive in group II (heterozygous) which was statistically significant. Conclusion: MTHFR C677T gene polymorphisms may play a role in unexplained infertility.

Women with Methylenetetrahydrofolate Reductase Gene Polymorphism and the Need for Proper Periconceptional Folate Supplementation

Maternal folate supplementation is critical for fetal development. Women with MTHFR （methylenetetrahydrofolate reductase） gene polymorphisms may not be getting the proper folate form to support fetal development. The objectives of this review were to： （1） undertake a comprehensive review on the association of MTHFR polymorphisms with the risk for various congenital diseases and other adverse pregnancy outcomes, （2） assess the efficacy and safety of current folic acid and other supplementations in women with the MTHFR polymorphism, and （3） provide guidance on the appropriate supplementation for women of childbearing potential with the MTHFR gene polymorphism in order to decrease these adverse pregnancy outcomes. Our assessments show that women with MTHFR gene polymorphism cannot efficiently convert folic acid to L-5-methyl-tetrahydofolate, the predominant active form of folic acid, due to reduced MTHFR enzymatic activity. L-5-methyl-tetrahydrofolate is currently commercially available under several brand names. Based on our comprehensive review and knowledge of the biochemistry of the folates, we recommend that L-5-methyltetrahydrofolate be given in combination with folic acid to women with MTHFR polymorphism that are pregnant or planning to become pregnant. Further study is needed to determine the optimal dose.

The common MTHFR C677T and A1298C variants are not associated with the risk of non-syndromic cleft lip/palate in northern Venezuela

Non-syndromic cleft lip with or without cleft palate （nsCL/P） is among the most common major birth defects, with complex inheritance involving multiple genes and environmental factors. Numerous studies of MTHFR, encoding methylenetetrahydrofolate reductase, which catalyzes the rate-limiting step of folic acid biosynthesis, have shown inconsistent association of two common hypomorphic allelic variants, C677T and A1298C, in nsCL/P patients and, in some cases, their mothers. We have studied the MTHFR C677T and A1298C polymorphisms in nsCL/P patients, their mothers, and population-matched controls from northern Venezuela. We found no evidence for contribution of the MTHFR C677T and A1298C variants to the risk of nsCL/P in northern Venezuela. Overall, our findings fail to support a causal role of either the MTHFR C677T or A 1298C variants in the pathogenesis of nsCL/P in northern Venezuela.

The combination of methylenehydrofolate reductase C677T polymorphism screening and gastrointestinal tumor markers detection may be an early screening method for gastrointestinal cancer related to helicobacter pylori infection

Methyltetrahydrofolate reductase(MTHFR)is a key enzyme in folate metabolism,and its single nucleotide polymorphism(SNP)site C677T may be associated with gastrointestinal cancer.However,the relationship between MTHFR C677T polymorphism and gastrointestinal tumor markers carcinoma embryonic antigen(CEA),carbohydrate antigen 199(CA199)and carbohydrate antigen 724(CA724)in Helicobacter pylori(H.pylori)infection is not specified.This study aims to identify the association between MTHFR C677T polymorphism and gastrointestinal tumor markers(CEA,CA199 and CA724)in H.pylori infection.The relationship between MTHFR C677T polymorphism and gastrointestinal tumor markers in 58 patients with H.pylori infection and 94 non-infected patients was studied.We found that TT genotype was a susceptibility factor of H.pylori infection,which was also associated with increased CEA and CA724 levels.Moreover,there was a negative additive interaction between MTHFR gene C677T polymorphism and CEA levels in H.pylori infection.Meanwhile,there were significant differences in CEA levels between MTHFR C677T polymorphism and H.pylori infection.The presence of T allele led to a decrease in CEA levels when ^(13)C urea breath test(^(13)C-UBT)was positive,while the presence of T allele led to an increase in CEA levels when ^(13)C-UBT was negative.Therefore,we suggest that healthy people should take MTHFR C677T polymorphism screening,combined with ^(13)C-UBT and gastrointestinal tumor markers detection,which can screen out the susceptible population of H.pylori,and help to detect gastrointestinal cancer in the early stage.

Effect of enalapril on plasma homocysteine levels in patients with essential hypertension

Objective:To investigate the effect of enalapril on plasma homocysteine(Hcy) levels and the association of methylenetetrahydrofolate reductase(MTHFR) C677T polymorphism with the changes of Hcy levels in response to enalapril among patients with essential hypertension.Methods:A total of 130 patients with mild-to-moderate essential hypertension were enrolled and enalapril was orally administered at a dose of 10 mg/d for eight weeks.Plasma Hcy levels were measured by denaturing high-performance liquid chromatography(DHPLC) at baseline and after eight weeks of treatment.Genotyping of MTHFR C677T polymorphism was performed by TaqMan probe technique.Results:Compared with baseline,plasma Hcy levels did not change significantly after eight weeks(P=0.81).Stratified by baseline Hcy levels,a significant increase in plasma Hcy levels(P=0.02) among those with Hcy <10 μmol/L was observed,in contrast to no significant changes in plasma Hcy levels(P=0.54) among those with Hcy ≥10 μmol/L.No significant association was observed between MTHFR C677T polymorphism and changes in Hcy levels in response to enalapril.Conclusions:Enalapril may cause an increase in plasma Hcy levels among the hypertensives with low baseline Hcy levels.There was no significant association between MTHFR C677T genotypes and changes in Hcy levels in response to enalapril among subjects with essential hypertension.