Association Of MTHFR C677T Polymorphism Research Articles

Association of MTHFR C677T polymorphism with risk of preterm birth in Indian mothers: a case–control study

BackgroundSince MTHFR is the key enzyme in folate metabolism, its reduction can lead to hyperhomocysteinemia, which can have a negative impact on pregnancy outcome. Moreover, MTHFR polymorphism has also been linked with oxidative stress and genotoxicity. Identifying its ethnicity-specific association can help to reduce the incidence of preterm birth (PTB). Material and methods: Age-matched preterm birth mothers (< 37 weeks) and full-term mothers (> 37 weeks) were carefully selected for the study. The polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method was adopted to analyse MTHFR C677T polymorphism. Oxidative stress (OS) analysis was performed by measuring the levels of antioxidants (superoxide dismutase (SOD) and catalase (CAT)) and OS damage markers (lipid peroxidation (LPO), total protein). Genotoxicity was confirmed by the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The statistical analysis was performed by Student’s t test, chi-square test, and one-way ANOVA. The relevant risk of premature delivery was represented by odds ratios (ORs) with 95% confidence intervals (95% CIs).ResultsThe MTHFR polymorphism showed statistical significance for PTB outcome with CT and TT genotype frequencies at p < 0.01 and p < 0.05, respectively, between cases and controls. Within the PTB categories (extreme-, very-, moderate-PTB), TT genotype showed statistical significance at (p < 0.05), while CT genotype remained insignificant. Also, statistically high oxidative stress and DNA damage were observed in cases compared to controls for all genotypes. Furthermore, the T allele of the MTHFR gene was found to be linked with significantly increased OS and DNA damage on comparison within the groups.ConclusionsThis study confirms the MTHFR C677T polymorphism, oxidative stress, and genotoxicity biomarkers are associated with the PTB outcome. Analysis of these biomarkers during pregnancy can be of clinical significance.

Evaluation of homocysteine, folic acid and methylenetetrahydrofolate reductase C677T gene polymorphism associated with recurrent spontaneous miscarriage

This study was aimed to assess the association between evaluation of homocysteine level, folic acid and methylenetetrahydrofolate reductase MTHFR C677T gene polymorphism and recurrent pregnancy loss RSA. Sixty four women diagnosed with RSA and 41 normal fertile female, who had at least one or more child, 21 of them were pregnant women while 20 were non-pregnant. The level of homocysteine was high in women with RSA (11.41+3.75) (p&lt;0.05) compared to normal fertile women either pregnant (7.02+2.13) or non-pregnant (6.84+2.08), low levels of folic acid was observed (6.35+2.09) in women with RSA (p&lt;0.05) compared to fertile women either pregnant(10.08+3.08) or non-pregnant(11.27+3.15). No statistically significant difference was observed in the distribution of genotypes between cases and controls for MTHFR polymorphism. In conclusion, the present study reveals to lack of association of MTHFR C677T polymorphism in RSA women.

Association Between MTHFR C677T Polymorphism and Susceptibility to Autism Spectrum Disorders: A Meta-Analysis in Chinese Han Population

Prior studies have examined the influence of MTHFR C677T on autism susceptibility, however, there are no consensus conclusions and specific analyses of a Chinese population. This meta-analysis included a false-positive report probability (FPRP) test to comprehensively evaluate the association of MTHFR C677T polymorphism with autism susceptibility among a Chinese Han population. A large-scale literature retrieval was conducted using various databases including PubMed, Embase, Wan Fang, and the Chinese National Knowledge Infrastructure (CNKI) up to July 31, 2020, with a total of 2,258 cases and 2,073 controls included. The strength of correlation was assessed by odds ratios (ORs) and 95% confidence intervals (95% CIs). MTHFR C677T showed a significant correlation with increased ASD susceptibility under all genetic models (T vs. C, OR = 1.89, 95% CI 1.28 to 2.79; TT vs. CC: OR = 2.44, 95% CI 1.43 to 4.15; CT vs. CC, OR = 1.73; 95% CI 1.19 to 2.51; CT + TT vs. CC: OR = 2.03, 95% CI 1.31 to 3.15; TT vs. CT + CC, OR = 1.95, 95% CI 1.21 to 3.13). Stratification analysis by region also revealed a consistent association in the Northern Han subgroup, but not in the Southern Han subgroup. Pooled minor allele frequency (MAF) of 30 studies were 45% in Northern Han and 39% in Southern Han. To avoid a possible “false positive report,” we further investigated the significant associations observed in the present meta-analysis using the FPRP test, which consolidated the results. In conclusion, MTHFR C677T polymorphism is associated with the increased risk of autism in China, especially in Northern Han. For those mothers and children who are generally susceptible to autism, prenatal folate and vitamin B12 may reduce the risk that children suffer from autism, especially in Northern Han populations. In the future, more well-designed studies with a larger sample size are expected.

Impact of MTHFR C677T and A1298C gene polymorphisms on MTX drug toxicity and efficacy profile of RA patients in North India

ObjectiveTo investigate the effect of two different methylenetetrahydrofolate (MTHFR) gene loci C677T and A1298C polymorphisms on Rheumatoid arthritis (RA) and their association in response to methotrexate (MTX) therapy. Subjects and methods110 individuals (60 RA patients and 50 healthy controls) were enrolled from different regions of north India. MTX drug response was evaluated by questionnaire data analysis, disease activity score (DAS-28) and analysis of hepatic, renal and other serological parameters. MTHFR C677T and A1298C polymorphisms were genotyped using restriction fragment length polymorphism- polymerase chain reaction (RFLP-PCR). Independent t-test was applied to compare the means and ANOVA with Bonferroni correction for multiple comparison of genotypically classified groups. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by applying χ2 test, p-value < .05 was considered significant. ResultsThe study found significant differences in all the serological parameters of controls and RA patients except protein and serum SGPT. Elevated transaminases, triglycerides, cholesterol, creatinine, C-reactive protein (CRP), uric acid and albumin are the indicators of MTX adverse effects along with disease severity. Questionnaire analysis showed loss of appetite, weak digestion, low BMI, and weight loss are common features in all the patients after starting MTX therapy. Significant association was found between 677TT genotype with elevated levels of triglycerides. While other parameters such as SGOT, SGPT, CRP, uric acid and cholesterol were insignificantly higher in patients with 677TT polymorphism. 1298CC polymorphism was associated with high CRP levels and 1298 AC with higher triglycerides along with cholesterol in RA patients. However, in controls, only albumin showed significant association with 1298AA genotype. Association of MTHFR C677T polymorphism was insignificant (677CT- OR: 0.905, 95%CI: 0.355–2.307; 677TT- OR: 1.035, 95%CI: 0.338–3.989; p-value = 1) and A1298C polymorphism was also insignificant (1298AC- OR: 0.562, 95%CI: 0.200–1.575, p-value = .4; & 1298CC- OR: 0.502, 95%CI: 0.146–1.717 with p-value = .403) with RA. ConclusionThe results of this study suggest that none of these alleles are predictive for RA disease susceptibility. However, it has a significant impact on its severity with respect to CRP, triglycerides and cholesterol.

Association of MTHFR C677T polymorphism with elevated homocysteine level and disease development in vitiligo.

Increasing evidence on the association of MTHFR gene polymorphism and serum homocysteine levels with autoimmune diseases such as vitiligo has made the MTHFR gene a very interesting candidate to be evaluated in different ethnicities and populations. We aimed to evaluate the levels of serum homocysteine and vitamin B12 and their associations with MTHFR C677T polymorphism in the Iranian population. This case-control study included 104 patients with vitiligo and 100 age- and sex-matched healthy control subjects. Serum vitamin B12 and homocysteine levels were measured by a chemiluminescence assay. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used for genotyping the polymorphism. The mean serum homocysteine levels were significantly higher in cases than controls and associated with disease activity (p<.001). Furthermore, the homozygous MTHFR C677T variant genotype was associated with vitiligo development (adjusted OR: 3.52, 95% CI: 1.09-11.32, p=.02) and elevated homocysteine level (p<.001). There was no association between serum vitamin B12 levels and the MTHFR C677T genotype. The homozygous variant MTHFR C677T may be considered as a risk factor for both elevated homocysteine levels and the development of vitiligo in the Iranian population. Although these results are not conclusive, they could elucidate the contribution of genetic and immune-mediated inflammatory factors to the pathogenesis of vitiligo.

Association of MTHFR C677T Polymorphism with Preeclampsia in North East of Iran (Khorasan Province)

Background: Preeclampsia (PE) is one of the main causes of fetal and maternal mortality. The analysis of candidate gene polymorphisms can improve our understanding of the mechanisms underlying pathogenesis of PE. Present study is aimed at investigating the association between MTRR c.66A > G, MTHFR c.677C > T, MTHFR c.1298A > C, and MTR c.2756A > G polymorphisms and PE in Iranian women. Methods: About 117 women with history of PE and 103 healthy women with a pregnancy not complicated by PE were selected. The genomic DNA was extracted from peripheral blood. Single-nucleotide polymorphisms were genotyped using Real-Time PCR. Results: There was a significant difference between MTHFR c.677C > T polymorphism with PE (p = 0.045). The frequency of C/T heterozygous genotypes were (58% vs. 36%) in the case and control groups, respectively. There were no statistically significant differences between other genetic polymorphisms. Conclusions: The results indicated that the MTHFR c.677C > T polymorphism may be associated with development of PE in Iranian women.

MTHFR gene (C677t) polymorphism in Ischemic stroke, its subtypes and hemorrhagic stroke in a South Indian population

Objective: We investigated the association of MTHFR C677T polymorphism with ischemic stroke, its subtypes and hemorrhagic stroke in a South Indian Population from Andhra Pradesh. Methods: Six hundred and twenty ischemic stroke patients, 220 hemorrhagic stroke patients and 620 age and sex matched healthy controls, were included in the present study. The polymorphism was determined using PCR-RFLP technique. Results: The strength of association between genotypes and stroke types was measured by the odds ratio with 95% confidence interval and chi-squared analysis. We found significant association of the CT genotype with ischemic stroke as well as haemorrhagic stroke (p

Association of MTHFR C677T Polymorphism with Susceptibility to Migraine in the Chinese population

A number of genes have been implicated in the pathogenesis of migraine, a common neurological disorder also in China. However, data on association of genetic variations with migraine susceptibility among Chinese, which might be different from people of other ethnic background, are still scarce. We have therefore investigated the association of polymorphisms in four genes, MTHFR C677T, ACE I/D, MAOA T941G and TNF-β G252A, which are considered to be with risk of migraine. A case–control study including a cohort of 151 migraine cases and 137 ethnically matched controls was conducted. The genotypes of each polymorphism followed the Hardy–Weinberg equilibrium in the two groups. Genotypic distribution of MTHFR C677T was significantly different with higher frequency of allele T in the migraine cohort as compared with that in controls (OR=1.686, 95%CI: 1.175–2.420, P=0.004). No difference was found between migraine with aura (MA) patients and controls, but T allele frequency was significantly higher in migraine without aura (MO) than in controls (OR=1.744, 95% CI: 1.202–2.532, P=0.003). No difference in genotypic and allelic distributions was observed between migraine patients and controls for the other polymorphisms, including ACE I/D, MAOA T941G, and TNF-β G252A. Our data suggested that MTHFR C677T polymorphism plays a role in Chinese migraine susceptibility, especially in MO.

Cervical cancer with polymorphism in MTHFR C677T gene: a systematic review and meta-analysis

To perform a meta-analysis investigating the association of MTHFR C677T polymorphism and susceptibility of cervical cancer. All case-control studies published in English and Chinese with estimates of the relationship between MTHFR C677T polymorphism and risk of cervical cancer were analyzed using odds ratio (OR) with 95 % confidence interval (CI). A total of 10 studies (2,023 cases and 2,570 controls) were included in the meta-analysis. No significant association was observed between T allele and C allele (OR = 0.90; 95 %CI = 0.70-1.17; P = 0.43), and for genotype TT versus CC (OR = 1.09; 95 %CI = 0.74-1.61; P = 0.67), CT versus CC (OR = 0.95; 95 %CI = 0.75-1.20; P = 0.65), CT + TT versus CC (OR = 0.91; 95 %CI = 0.66-1.24; P = 0.55). The current meta-analysis results suggest that the MTHFR C677T polymorphism may not be associated with cervical cancer.

Colorectal cancer and polymorphism of methylenetetrahydrofolate reductase (C677T) in Morocco

Introduction Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. It is involved in the synthesis, repair, and methylation of deoxyribonucleic acid (DNA). The most frequently studied MTHFR gene polymorphism is C677T, which is involved in the pathogenesis of many diseases including cancer. This case-control study was undertaken to analyze the association of MTHFR C677T polymorphism and the risk of colorectal cancer (CRC).

Association between MTHFR C677T polymorphism and osteonecrosis of the femoral head: a meta-analysis

The results of studies on association between the C677T polymorphism of the 5,10-methylene-tetrahydrofolate reductase (MTHFR) gene and osteonecrosis of the femoral head (ONFH) are controversial. To derive a more precise estimation of the relationship between the MTHFR C677T polymorphism and ONFH, a meta-analysis was performed. Eight studies on MTHFR C677T association with ONFH were searched up to April 2011, and the genotype frequencies in control group were consistent with Hardy-Weinberg equilibrium. The effect summary odds ratio (OR) and 95% confidence intervals were obtained. Publication bias was tested by funnel plot, Egger's regression test, and heterogeneity was assessed. Eight studies containing 778 cases and 1,162 controls were included. Heterogeneity was observed (χ(2) = 18.58, P = 0.01). Under the random effects model, the common OR was 1.38 (95% CI: 0.92-2.08; P = 0.12). In the subgroup meta-analysis, there was an association between MTHFR C677T polymorphism and ONFH in non-Asian population for CT + TT vs. CC (OR = 1.72; 95% CI: 1.21-2.43; P = 0.002; I(2) = 37.9%, P = 0.17), but not for Asian population (OR = 0.88; 95% CI: 0.66-1.66; P = 0.35; I(2) = 45.4%, P = 0.16). There was heterogeneity between studies and no clear evidence of an association on a worldwide population. When stratifying for the race, this meta-analysis did not provide an evidence of confirming association between MTHFR C677T polymorphism and ONFH. The large sample and well-designed study based on different ethnic groups should be considered in future associated studies to clarify the association of MTHFR C677T polymorphism with ONFH susceptibility.

MTHFR C677T polymorphism is associated with hyperlipidemia in women with polycystic ovary syndrome

CONTEXT:Women with polycystic ovary syndrome (PCOS) are prone for coronary artery disease (CAD), and hyperhomocysteinemia is an independent risk factor for CAD. MTHFR deficiency is the most common cause of hyperhomocysteinemia, thereby provoking a possible association between PCOS and MTHFR C677T polymorphism.AIMS:The aim of this study was to investigate an association of MTHFR C677T polymorphism with PCOS.SETTINGS AND DESIGN:92 women with PCOS (Rotterdam criteria) and 95 age-matched controls were compared with respect to MTHFR C677T polymorphism. The 2 genotypes (CC and CT) obtained were compared with clinical and laboratory parameters in women with PCOS.MATERIALS AND METHODS:In a case-control study, clinical, biochemical, hormonal and genetic analysis (PCR-RFLP of peripheral leucocytes) was carried out on all women with PCOS as well as controls.STATISTICAL ANALYSIS:Student “t” test for quantitative and Chi-square test for nominal variables was used. For estimation of risk, odds ratio and 95% confidence interval were calculated.RESULTS:The odds ratio of bearing a heterozygous genotype (CT) was 1.32 in women with PCOS as compared to controls (P = 0.48). No homozygous mutation (TT) was found in the study population. Serum cholesterol was more in heterozygous (CT) genotype (215.48 ± 25.56 mg/dl) as compared to normal (CC) genotype (203.29 ± 16.35 mg/dl) in women with PCOS (P = 0.01). Similarly, serum triglyceride was more in heterozygous (CT) genotype (95.86 ± 37.34 mg/dl) as compared to normal (CC) genotype (82.36 ± 20.88 mg/dl) in women with PCOS (P = 0.04).CONCLUSIONS:Although not statistically significant, there is a slightly higher prevalence of heterozygous (CT) genotype in women with PCOS. MTHFR C677T polymorphism when present may confer an increased susceptibility to develop hyperlipidemia in women with PCOS. More prospective studies are needed to confirm whether this hyperlipidemia due to MTHFR C677T polymorphism clinically manifests into CAD in long term in women with PCOS.