Methylenetetrahydrofolate Reductase A1298C Polymorphisms Research Articles

Skin disorders in women with poor obstetric history: MTHFR polymorphisms and importance of preconceptional counseling

Background This study focused on the link between skin disorders and Methylenetetrahydrofolate reductase (MTHFR) polymorphisms. Methods Study cases were taken from a pre-conceptional care program where patients with poor obstetric history were evaluated in terms of systemic disorders including skin diseases. This retrospective cohort (n = 472) consisted of 110 (23.3%) and 362 (76.7%) women with or without skin disorders, respectively. For ease of analysis, the history of skin diseases was classified into seven categories: 1) acne/rosacea/other acneiform disorders; 2) fungal disease; 3) pruritis/xerosis; 4) psoriasis vulgaris; 5) acrochordons and other benign skin growths; 6) urticaria/dermatitis; and 7) viral diseases. Results In this retrospective cohort of 472 women, we explored the impact of MTHFR A1298C and C677T polymorphisms on skin disorders. Despite similar allelic frequencies, our findings revealed a statistically significant association between the presence of MTHFR polymorphisms and skin disorders (p = 0.027). Subgroup analysis indicated significantly higher rates of MTHFR polymorphisms in patients with psoriasis vulgaris (p = 0.033) and acrochordons (p = 0.030), highlighting their potential relevance in specific skin disorder subtypes. Conclusions The increased prevalence of psoriasis and acrochordons among women with MTHFR deficiency underscores the complex relationship between genetic factors and dermatological health. Our findings emphasized the critical role of MTHFR polymorphisms not only in poor obstetric history but also as significant contributors to skin disorders. This dual association highlights the importance of comprehensive preconception counseling, especially customized for women affected by skin disorders.

Prevalence of MTHFR Polymorphisms in Patients With Hypermobile Ehlers-Danlos Syndrome and Hypermobile Spectrum Disorders in a US Hypermobility Clinic.

Hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are characterized by joint hypermobility, joint subluxations and dislocations, hyperextensible skin, and chronic and progressive multiorgan comorbidities. Diagnosing hEDS and HSD is difficult because of variable phenotypes and unknown genetic etiology. In our clinic, we observed many patients with hEDS and HSD with a high serum level of unmetabolized folate, which suggests that hypermobility may be linked to methylenetetrahydrofolate reductase (MTHFR)-mediated folate metabolism. The present study aims to examine the prevalence of MTHFR polymorphisms, C677T and A1298C, among patients with hEDS and HSD. Clinical and demographic information of patients visiting our hypermobility clinic from January 2023 to July 2023 were retrospectively reviewed. Continuous variables were reported as mean ± SD and range, whereas categorical variables were reported as total count and percentage. Among 157 patients, 93% of patients were female patients, 52.2% were diagnosed with hEDS, and 47.8% were diagnosed with HSD. Interestingly, 85% of the patients had MTHFR C677T and/or A1298C polymorphisms in heterozygous or homozygous state. MTHFR 677CT/TT genotype was present in 52.9% of cases, and 49.7% of patients had 1298AC/CC genotype. In addition,14% of patients with hypermobility exhibited MTHFR 677TT genotype, 10.2% showed 1298CC genotype, and 17.2% displayed combined heterozygosity, collectively representing 41.4% hypermobile patients with two copies of MTHFR variant alleles. There is a high prevalence of MTHFR polymorphisms among patients with hypermobility, which supports the hypothesis that hypermobility may be dependent on folate status.

Interaction effects of MTHFR C677T and A1298C polymorphisms with maternal glycated haemoglobin levels on adverse birth outcomes.

The role of maternal genetic factors in the association between high glycated haemoglobin (HbA1c) levels and adverse birth outcomes remains unclear. In this study, the maternal HbA1c levels of 5108 normoglycemic pregnant women in China were measured, and A1298C and C677T polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene were genotyped. Elevated HbA1c levels during the second trimester were associated with increased risks of macrosomia, large-for-gestational age (LGA), preterm birth (PTB), and reduced gestational age (p<0.05). Pregnant women with MTHFR A1298C AA or C677T CT+TT genotypes were susceptible to adverse pregnancy outcomes related to HbA1c levels. Among pregnant women with the A1298C AA genotype, each standard deviation (SD) increase in HbA1c levels increased the risk of PTB by 1.32-times and reduced the gestational age by 0.11weeks (p<0.05). For MTHFR C677T CC+TT genotype carriers, higher HbA1c levels were associated with 1.49-, 1.24-, and 1.23-times increased risks of macrosomia, LGA, and PTB, respectively (p<0.05). A U-shaped curve for PTB risk in relation to HbA1c levels was observed among the C677T CC+TT participants, with a cut-off value of 4.58%. Among subjects with the A1298C AA genotype combined with the C677T CT+TT genotype, each SD increase in HbA1c levels was associated with 1.40 and 1.37-times increased risks of LGA and PTB, respectively. Our findings highlight the importance of glycaemic control during pregnancy and the potential impact of genetic factors on birth outcomes. However, further large-scale studies are required to confirm these findings.

MTHFR gene polymorphisms and susceptibility to myocardial infarction: Evidence from meta-analysis and trial sequential analysis

BackgroundThis meta-analysis aimed to provide a comprehensive assessment of the association between Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, specifically C677T and A1298C, and the susceptibility to myocardial infarction (MI). MethodsA systematic literature search was conducted in MEDLINE, Web of Science, and Scopus until April 2023 to identify studies investigating the relationship between MTHFR gene polymorphisms (C677T and A1298C) and the risk of MI. ResultsThe analysis included 66 studies involving 16,860 cases and 20,403 controls for the C677T polymorphism and 18 studies comprising 3162 cases and 3632 controls for the A1298C polymorphism. Significant associations were observed between the C677T polymorphism and MI risk in various genetic models: dominant (OR = 1.16, 95 % CI = 1.06–1.28, P = 0.008), recessive (OR = 1.20, 95 % CI = 1.12–1.28, P < 0.001), allelic (OR = 1.13, 95 % CI = 1.06–1.21, P < 0.001), TT vs. CC (OR = 1.19, 95 % CI = 1.05–1.36, P < 0.001), and CT vs. CC (OR = 1.11, 95 % CI = 1.02–1.21, P = 0.01). Furthermore, an overall analysis indicated a marginally significant association between the A1298C polymorphism and MI risk in the recessive model (OR = 1.27, 95 % CI = 1.06–1.51, P = 0.008), allelic model (OR = 1.18, 95 % CI = 1.01–1.39, P = 0.03), and CC vs. AA model (OR = 1.22, 95 % CI = 1.01–1.47, P = 0.04). Meta-regression analysis revealed that none of the potential factors contributed to the observed heterogeneity. ConclusionsThis meta-analysis revealed an association between MTHFR gene C677T and A1298C polymorphisms and the risk of MI.

Association Between MTHFR Gene Polymorphism (A1298c) C&gt;A and Sensitivity to Cervical Cancer: A Meta-Analysis

We have investigated the association between methylenetetrahydrofolate reductase A1298C polymorphism and cervical cancer. A comprehensive search was conducted in Wanfang, China HowNet and PubMed databases to retrieve Chinese and English literature from the construction of the database to December 2019. Stata software was utilized to conduct the analysis of the five genetic models, while the odds ratio and 95% confidence interval were employed to assess the correlation. 12 pertinent publications were included with 3839 subjects (1546 patients and 2293 healthy control). There were no significant associations between A1298C and cervical cancer risk under recessive model, dominant model, allele model, co-dominant model. In the sub-analysis by ethnic groups, a significant association between A1298C and cervical cancer risk under recessive model in Asia. It is suggested a potential association between methylenetetrahydrofolate reductase gene polymorphism A1298C and an elevated susceptibility to cervical cancer in the Asian population, specifically under the recessive model.

MTHFR C677T and A1298C polymorphism’s effect on risk of colorectal cancer in Lynch syndrome

Lynch syndrome (LS) is characterised by an increased risk of developing colorectal cancer (CRC) and other extracolonic epithelial cancers. It is caused by pathogenic germline variants in DNA mismatch repair (MMR) genes or the EPCAM gene, leading to a less functional DNA MMR system. Individuals diagnosed with LS (LS individuals) have a 10–80% lifetime risk of developing cancer. However, there is considerable variability in the age of cancer onset, which cannot be attributed to the specific MMR gene or variant alone. It is speculated that multiple genetic and environmental factors contribute to this variability, including two single nucleotide polymorphisms (SNPs) in the methylenetetrahydrofolate reductase (MTHFR) gene: C677T (rs1801133) and A1298C (rs1801131). By decreasing MTHFR activity, these SNPs theoretically reduce the silencing of DNA repair genes and increase the availability of nucleotides for DNA synthesis and repair, thereby protecting against early-onset cancer in LS. We investigated the effect of these SNPs on LS disease expression in 2,723 LS individuals from Australia, Poland, Germany, Norway and Spain. The association between age at cancer onset and SNP genotype (risk of cancer) was estimated using Cox regression adjusted for gender, country and affected MMR gene. For A1298C (rs1801131), both the AC and CC genotypes were significantly associated with a reduced risk of developing CRC compared to the AA genotype, but no association was seen for C677T (rs1801133). However, an aggregated effect of protective alleles was seen when combining the alleles from the two SNPs, especially for LS individuals carrying 1 and 2 alleles. For individuals with germline pathogenic variants in MLH1, the CC genotype of A1298C was estimated to reduce the risk of CRC significantly by 39% (HR = 0.61, 95% CI 0.42, 0.89, p = 0.011), while for individuals with pathogenic germline MSH2 variants, the AC genotype (compared to AA) was estimated to reduce the risk of CRC by 26% (HR = 0.66, 95% CI 0.53, 0.83, p = 0.01). In comparison, no association was observed for C677T (rs1801133). In conclusion, our study suggests that combining the MMR gene information with the MTHFR genotype, including the aggregated effect of protective alleles, could be useful in developing an algorithm that estimates the risk of CRC in LS individuals.

No association between MTHFR gene C677T/A1298C polymorphisms, serum folate, vitamin B12, homocysteine levels, and prostate cancer in an Algerian population.

Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate and homocysteine metabolism, which are necessary for DNA methylation and nucleotide synthesis. Genetic polymorphisms that reduce MTHFR activity have been linked to several diseases, including prostate cancer. In this study, we aimed to investigate whether MTHFR polymorphisms, along with serum levels of folate, vitamin B12, and homocysteine, are associated with prostate cancer risk in the Algerian population. A total of 106 Algerian men with newly diagnosed prostate cancer and 125 healthy controls were included in this case-control study. The MTHFR C677T and A1298C polymorphisms were analyzed using PCR/RFLP and Real-Time PCR TaqMan® assays, respectively. Serum levels of folate, total homocysteine, and vitamin B12 were measured using an automatic biochemistry analyzer. We found no significant differences in the genotype frequency of A1298C and C677T between prostate cancer patients and controls. Moreover, serum levels of folate, total homocysteine, and vitamin B12 were not significantly associated with prostate cancer risk (p > 0.05). However, age and family history were identified as significant risk factors (OR = 1.178, p = 0.00 and OR = 10.03, p = 0.007, respectively). Our study suggests that MTHFR C677T and A1298C, as well as serum levels of folate, total homocysteine, and vitamin B12, are not associated with prostate cancer risk in the Algerian population. However, age and family history are significant risk factors. Further studies with a larger sample size are required to confirm these findings.

MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid Arthritis.

Methotrexate (MTX) is used as an anchor drug for the treatment of rheumatoid arthritis (RA) and there may be differences in drug action between genotypes. The purpose of this study was to investigate the relationship between clinical efficacy response and disease activity of MTX monotherapy with methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms. In the study, a population of 32 patients in East China with early RA fulfilling the diagnostic standards of the American College of Rheumatology (ACR) were enrolled, all of them received MTX monotherapy. Genotyping of patients MTHFR C677T and A1298C, MTRR A66G using tetra-primer ARMS-PCR method and sanger sequencing to verify its accuracy. The distribution of three polymorphic genotypes that were studied is in accordance with the Hardy-Weinberg genetic equilibrium. The patient pathology variables smoke (OR = 0.088, P = 0.037), drink alcohol (OR = 0.039, P = 0.016) and males (OR = 0.088, P = 0.037) were significantly associated with non-response to MTX. Genotype, allele distribution and genetic statistical models were not found to be related to MTX treatment response and disease activity in both the response groups and non-response groups. Our findings suggest that the MTHFR C677T, MTHFR A1298C and MTRR A66G polymorphisms may not predict MTX clinical treatment response and disease activity in patients with early RA. The study revealed that smoke, alcohol, and males were possible influential factors for MTX non-response.

Synergistic effect of MTHFR polymorphisms in arterial ischemic stroke in young adult (P3-5.014)

<h3>Objective:</h3> Aims to evaluate the effect of methylenetetrahydrofolate reductase (MTHFR) polymorphisms (C677T and A1298C) in arterial ischemic stroke (AIS) among young patients. <h3>Background:</h3> The imputability of MTHFR polymorphisms in the occurrence of AIS remains ambiguous currently. <h3>Design/Methods:</h3> Blood samples were collected from patients and healthy controls aged under 50 years from Tunisia, from January 2015 to December 2019. Statistical analysis was carried out to evaluate the relationship between MTHFR polymorphisms and AIS occurrence. <h3>Results:</h3> A total of 275 cases including 161 patients and 114 healthy controls, all matched for age and gender. The mutant genotypes of MTHFR C677T polymorphisms were found to significantly increase the risk of AIS (p&lt; 10–3). Besides, the CC genotype of MTHFR A1298C polymorphism is significantly more prevalent in the pathologic group when compared to controls (OR: 3.471; 95% CI [1.594–7.557], p &lt; 0.005). regarding the synergistic effect of both MTHFR (C667T/A1298C) polymorphisms, the TT /AA and TT/AC genotype was significantly associated with AIS (OR: 2.225; 95%CI [1.984–5.032] and 2.832 95%CI [1.613–13.091] respectively). The CC/CC genotype was not associated with stroke (p = 0.26). The compound genotype of CT/AC revealed a 4.98-fold increased risk for AIS (OR: 4.98; 95%CI [2.016–12.336]). <h3>Conclusions:</h3> Our study confirmed the involvement of MTHFR polymorphisms as AIS’s important risk factors. We assume that the synergistic effect of both MTHFR polymorphisms increases the risk of the AIS. <b>Disclosure:</b> Miss M’barek has nothing to disclose. khadija maalla has nothing to disclose. Nadia Bouattour has nothing to disclose. Sawsan Daoud has nothing to disclose. Nouha Farhat has nothing to disclose. mariem damak has nothing to disclose. Salma Sakka has nothing to disclose. Prof. Mhiri has received personal compensation for serving as an employee of Hikma. Prof. Mhiri has received personal compensation for serving as an employee of Sanofi Genzyme. Prof. Mhiri has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Prof. Mhiri has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche.

Association of Methylenetetrahydrofolate Reductase Gene Polymorphism in Mothers With Adverse Clinical Outcomes in Neonates.

The presence of polymorphic methylenetetrahydrofolate reductase(MTHFR) in mothers poses a risk for numerous detrimental outcomes in neonates. The present study investigated the association of maternal MTHFR A1298C and C677T single nucleotide polymorphisms (SNPs) with the clinical outcomes in their neonates. The cross-sectional study included 60 mothers and their neonates. Blood samples from mothers were analyzed for MTHFR A1298C and C677T SNP genotyping by real-time polymerase chain reaction. Clinical details of mothers and neonates were documented. Study groups were stratified based on wild, heterozygous, and mutant genotypes for the respective polymorphisms observed in mothers. Multinomial regression was applied for the association, followed by gene model formulation to estimate the impact of the genetic variants on the outcomes. The frequency percentages of mutant CC1298 and TT677 genotypes were 25% and 8.06%, respectively, and the mutant allele frequencies (MAF) were 42.5% and 22.5%. Percentages of adverse outcomes such as intrauterine growth restriction, sepsis, anomalies, and mortality were higher in neonates born to mothers with homozygous mutant genotypes. Maternal C677T MTHFR SNPs revealed a significant association with neonatal anomalies (p = 0.001). The multiplicative risk model depicted OR (95% CI) for CT vs. CC+TT as 3.0 (95% CI: 0.66-13.7), and for TT vs. CT+CC was 15 (95% CI: 2.01-112.12). The C677T SNP in mothers predicted a dominant model for neonatal death (OR (95% CI): 5.84 (0.57-60.03), p = 0.15), whereas the A1298C reported recessive model for 1298CC mothers (OR (95% CI): 11 (1.05-115.5), p = 0.02). Both the genotypes assumed a recessive model for adverse neonatal outcomes: OR (95%CI) for CC vs. AA+ACwas 3.2 (0.79-12.9, p = 0.1), and for TT vs. CC+CT was 5.48 (0.57-175.7, p = 0.2). The risk for sepsis in neonates was nearly six times higher in those born from mothers with homozygous CC1298 and TT677 than in the wild and heterozygous variants. Mothers with C677T and A1298C SNPs are highly susceptible to adverse outcomes in their neonates. Hence, screening the SNPs during the antenatal period can purposefully serve as a better predictive marker, following which proper clinical management could be planned.

Methylenetetrahydrofolate reductaseC677T and A1298Cpolymorphisms and gastric cancer susceptibility: an updated meta-analysis.

Widely regarded as one of the most prevalent malignancies worldwide, gastric cancer(GC) is a common clinical condition of the digestive system.Reviewing14 meta-analyses that evaluated the association between Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and GC risk, we observed inconsistent results, and the credibility of the significant correlation between the statistical results was ignored. With the aim of further exploring the association between MTHFRC677Tand CA1298Cand the risk of GC, we searched electronic databases, pooling 43 relevant studies and calculating odds ratios (ORs)and corresponding 95% confidence intervals (CIs)for each of the five genetic models. Subgroup and regression analyses were performed to look for sources of heterogeneity and publication bias was assessed by funnel plots.To assess the plausibility of statistically significant associations, we used the FPRP test and the Venice criteria. Overall data analysis showed that MTHFRC677Tpolymorphismwas significantly associated with GC risk, especially in Asians, while MTHFRCA1298Cpolymorphism was not associatedwith GC risk. However, insubgroup analysisby hospital-based controls, we found that MTHFRCA1298Cmight be a protective factor for GC. After credibility assessment, the statistical association between MTHFRC677Tand GCsusceptibility study was classified as "less credible positive result", while the result of MTHFRCA1298Cwas considered unreliable.In summary, this study strongly suggests that MTHFR, C677Tand CA1298Cpolymorphisms are not significantly associated with the GC risk.

Genes predisposing tunneled catheter thrombosis in hemodialysis patients.

This study aims to investigate the association of genes predisposing thrombophilia with tunneled catheter thrombosis in hemodialysis patients. Between October 2018 and December 2020, we compared the frequencies of genetic polymorphisms causing thrombophilia, including prothrombin G20210A, factor V Leiden, methylene tetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, plasminogen activator inhibitor (PAI), factor XIII V34L and clinical characteristics of 52 patients with a history of 2 tunneled2 tunneled catheter thrombosis occlusions within a year (Group 1; 24 males, 28 females; mean age: 62±8.9 years; range, 45 to 77 years), 52 patients who underwent their first tunneled catheter thrombosis insertion (Group 2; 29 males, 23 females; mean age: 63±15.2 years; range, 22 to 87 years), and 51 healthy controls (Group 3; 26 males, 25 females; mean age: 34±9.2 years; range, 19 to 54 years). Groups 1 and 2 carried the MTHFR A1298C (p=0.048) and compound heterozygous MTHFR A1298C and C677T (p=0.048) polymorphisms more frequently than Group 3. However, subgroup analysis results were not statistically significant. The other polymorphisms were distributed similarly in all three groups. The MTHFR polymorphisms had a weak effect on tunneled hemodialysis catheter thrombosis in neural network analysis. Our study results indicated that there was a concomitance of MTHFR polymorphisms with hemodialysis-dependent chronic kidney disease. The MTHFR A1298C and compound heterozygous MTHFR polymorphisms may be associated with tunneled hemodialysis catheter thrombosis. Thrombophilia gene screening may be recommended in hemodialysis patients undergoing tunneled hemodialysis catheter thrombosis at least twice in a year.

The Association of Methylenetetrahydrofolate Reductase (MTHFR) A1298C Gene Polymorphism with Susceptibility to Diabetic Nephropathy: A Meta-Analysis.

This meta-analysis was conducted to investigate the association between MTHFR A1298C polymorphism and susceptibility to diabetic nephropathy. PubMed, Embase, Web of Science, Cochrane Library, China national knowledge infrastructure (CNKI) and China Wanfang database were searched for studies on the association between MTHFR A1298C single nucleotide polymorphism and susceptibility to diabetic nephropathy until May 2022. Data were analyzed by Stata 15.0 software. Odds ratio (OR) was used as the effect size. A total of 7 articles were identified, including 1287 cases in the diabetic nephropathy group and 1431 cases in the control group. The pooled OR of allele C at MTHFR A1298C was 1.28 (95% CI: 1.02-1.59, p=0.03) compared with allele A. The pooled OR values of dominant, and heterozygous genetic models were 1.45 (95% CI: 1.13-1.86), and 1.42 (95% CI: 1.19-1.70), respectively, and the differences were all statistically significant. There was no statistical significance in the recessive (OR=1.06, 95% CI: 0.62-1.82), and homozygous gene inheritance models (OR=1.29, 95% CI: 0.72-2.31). In conclusion, MTHFR A1298C polymorphism is associated with susceptibility to diabetic nephropathy. Allele C, genotype CC+AC, and AC at MTHFR A1298C locus can increase the risk of diabetic nephropathy.

Polymorphisms in gene MTHFR modify the association between gestational weight gain and adverse birth outcomes.

Evidence suggests a potential relationship between gestational weight gain (GWG) and adverse birth outcomes. However, the role of maternal genetic polymorphisms remains unclear. This study was conducted to investigate whether the relationship of GWG with risk of adverse birth outcomes was modified by methylenetetrahydrofolate reductase (MTHFR) polymorphisms. A total of 2,967 Chinese pregnant women were included and divided into insufficient, sufficient, and excessive groups based on the Institute of Medicine (IOM) criteria. Polymorphisms of C677T and A1298C in gene MTHFR were genotyped. Multivariable logistic regression models were introduced after controlling major confounders. Excessive GWG was found to increase the odds ratio (OR) for macrosomia [OR = 3.47, 95% confidence interval (CI): 1.86–6.48] and large-for-gestational age (LGA, OR = 3.25, 95% CI: 2.23–4.74), and decreased the OR for small-for-gestational age (SGA, OR = 0.60, 95% CI: 0.45–0.79). Pregnant women with insufficient GWG had a higher frequency of SGA (OR = 1.68, 95% CI: 1.32–2.13) and a lower rate of LGA (OR = 0.51, 95% CI: 0.27–0.96). Interestingly, significant associations of GWG categories in relation to low birth weight (LBW), macrosomia, and SGA were only suggested among pregnant women with MTHFR A1298C AA genotype. Among pregnant women with insufficient GWG group, an increased risk of 3.96 (95% CI: 1.57–10.01) for LBW was observed among subjects with the A1298C AA genotype, compared to the AC+CC genotype group. GWG categories are closely related to LBW, macrosomia, SGA and LGA, and the associations were modified by the polymorphism of MTHFR A1298C.

Associations of Two Common Polymorphisms in MTHFR Gene with Blood Lipids and Therapeutic Efficacy of Simvastatin.

Cardio-cerebrovascular disease is an important public health challenge worldwide, and its complex etiology has not been elucidated fully. The study investigated the relationship between two common polymorphisms, C677T and A1298C in the methylenetetrahydrofolate reductase (MTHFR) gene, baseline lipids and the lipid-lowering efficacy of simvastatin in a Chinese hyperlipidemic population. All participants were recruited from Anhui, China. By the extreme sampling method, we selected subjects with a low response (n=108) and high response (n=106) based on their adjusted lipid-lowering response to simvastatin administrated for 8 consecutive weeks. Both MTHFR C677T and A1298C loci were genotyped by the MALDI-TOF MS platform. Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured at baseline and after 8 weeks of oral 20 mg/d tablets of simvastatin. Patients with the 677TT genotype had significantly higher baseline TC, HDL-C, and change in HDL-C (ΔHDL-C) levels after treatment than those with 677CC+CT genotypes (β = 0.207, P = 0.045; β = 0.182, P = 0.026; and β = 0.16, P = 0.002, respectively). Patients with 1298AC+CC genotypes had significantly higher baseline LDL-C and change in LDL-C (ΔLDL-C) levels (β = 0.276, P =0.043; β = 0.359, P = 0.025, respectively) than those with 1298AA genotype. We found statistical interactions between the two SNPs in association with baseline HDL-C (P for interaction = 0.034), TC (P for interaction = 0.069), and TG (P for interaction = 0.034). Baseline TC (P = 0.027) and HDL-C (P = 0.046) and change in HDL-C (P = 0.019) were different among those with the MTHFR A-T haplotype compared with A-C. Our major findings suggest that both MTHFR C677T and A1298C polymorphisms could be important genetic determinants of lipid traits and drug efficacy of simvastatin. This will contribute to a better understanding of strategies for personalized medication in Chinese patients with dyslipidemia.

Methylene-tetrahydrofolate reductase gene C677T and A1298C polymorphisms as a risk factor for Crimean-Congo hemorrhagic fever

Crimean-Congo hemorrhagic fever (CCHF) is a deadly viral disease. Methylene-tetrahydrofolate reductase (MTHFR) has an important role in folate metabolism, and also in the formation of new cells, DNA synthesis, repair and methylation. We aimed to examine the relationship between MTHFR gene C677T (Ala222Val, rs1801133) and A1298C (Glu429Ala, rs1801131) polymorphisms with CCHF in a Turkish population. Totally 273 participants were included in the current study. One hundred forty-one participants were CCHF patients and one hundred thirty-two participants were healthy controls. The polymerase chain reaction (PCR) and further restriction fragment length polymorphism (RFLP) assays were applied to determine the genotypes of MTHFR polymorphisms. We did not find any differences between the CCHF patients and healthy controls in terms of allele and genotype distributions of both the C677T and A1298C polymorphisms. In composite genotype analysis between different groups, the frequency of CT-AA composite genotype, which is formed by C677T-A1298C polymorphisms, was found to be significantly higher in Mild CCHF patients compared to both Severe CCHF patients and controls (p = 0.036 and p = 0.008, respectively). In conclusion, in this study, we found a relationship between CCHF and MTHFR gene polymorphisms. CT-AA composite genotype of MTHFR gene C677T and A1298C polymorphisms showed a predisposition to Mild CCHF.

MTHFR C677T (rs1801133) genetic polymorphism is associated with development risk of essential hypertension in the Turkish population

BackgroundHypertension is a serious condition that is spread worldwide and may lead to severe complications such as heart attack, stroke, hypertensive retinopathy, and renal failure. Although some genetic and environmental risk factors are known to play a role in the etiology of hypertension, like most of the other multi-factorial diseases, its etiology is yet to be fully elucidated. Our study aimed to investigate the effects of methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) and A1298C (rs1801131), factor V Leiden (FVL) G1691A (rs6025), and prothrombin (PT) G20210A (rs1799963) genetic polymorphisms on the development risk of essential hypertension and level of blood pressure in hypertensive patients.ResultsThe frequency of the homozygous polymorphic TT genotype for the MTHFR C677T polymorphism was significantly higher in male hypertensive patients than in the male control group (27% vs 6.3%, p = 0.028). The rate of the variant T allele for the MTHFR C677T polymorphism was also significantly higher in male hypertensive patients compared to male healthy controls (51.4% vs 21.9%, p = 0.0004). There was no difference among hypertensive patients and healthy controls regarding the frequencies of MTHFR A1298C, FVL G1691A and PT G20210A polymorphisms. In addition, we found no difference between genotype groups regarding systolic and diastolic blood pressure levels in hypertensive patients.ConclusionsHomozygous polymorphic TT genotype and variant T allele for the MTHFR C677T polymorphism may be considered as a risk factor for the development of essential hypertension in the Turkish male population.

Association between FVL G1691A, MTHFR C677T and A1298C Polymorphisms with Risk for Retinopathy of PrematurityAssociation between FVL G1691A, MTHFR C677T and A1298C Polymorphisms with Risk for Retinopathy of Prematurity

Background: Retinopathy of prematurity (ROP) is an important cause of preventable blindness in children. The aim of this study was to examine the association of the polymorphisms at Factor V Leiden (FVL) and methylene tetrahydrofolate reductase (MTHFR) gene with risk of ROP.&#x0D; Methods: A total of 106 neonates with ROP and 110 healthy neonates were enrolled. The FVL G1691A and MTHFR C677T and A1298C polymorphisms were genotyped by PCR-RFLP assay.&#x0D; Results: There was a significant association between FVL G1691A polymorphism and an increased risk of ROP. However, the MTHFR C677T and A1298C polymorphisms were not associated with risk of ROP.&#x0D; Conclusion: FVL G1691A polymorphism may be risk factor for development of ROP in neonates. However, there was no significant association between MTHFR C677T and A1298C polymorphisms and risk of ROP. However, it is critical that larger and well-designed studies in different ethnicities are needed to confirm our conclusions.

Methylene tetrahydrofolate reductase A1298C polymorphisms influence the adult sequelae of chemotherapy in childhood-leukemia survivors.

This retrospective correlation study investigated the putative link between methylene tetrahydrofolate reductase (MTHFR) A1298C mutations and chemotherapy-related brain function changes in adult childhood-leukemia survivors. To this end, we determined the relationship between the particular MTHFR1298 genotype (AA, AC or CC) of 31 adult childhood-leukemia survivors, and (1) their CSF Tau and phosphorylated Tau (pTau) levels at the time of treatment, (2) their adult performance intelligence quotient (PIQ), and (3) their regional brain connectivity using diffusion magnetic resonance imaging (dMRI) and resting-state functional MRI (rsfMRI). We confirmed that neuropathology markers Tau and pTau significantly increased in CSF of children after intrathecal methotrexate administration. Highest concentrations of these toxicity markers were found during the induction phase of the therapy. Moreover, CSF concentrations of Tau and pTau during treatment were influenced by the children's particular MTHFR1298 genotype. CSF Tau (but not pTau) levels significantly dropped after folinic acid supplementation. At adult age (on average 13.1 years since the end of their treatment), their particular MTHFR1298 genotype (AA, AC or CC) influenced the changes in PIQ and cortical connectivity that we found to be related to their childhood exposure to chemotherapeutics. In summary, we suggest that homozygous MTHFR1298CC individuals are more vulnerable to the adult sequelae of antifolate chemotherapy.

Association of C677T (rs1081133) and A1298C (rs1801131) Methylenetetrahydrofolate Reductase Variants with Breast Cancer Susceptibility Among Asians: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis were conducted to investigate the association between methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms with breast cancer (BC) in Asians. Systematic searches were conducted in PubMed, EMBASE, Web of Science, and Scopus by May 2020. Inter-study heterogeneity was also assessed with a Q test, along with I2 statistics. Random-effects models were applied to pooled crude ORs with corresponding 95% CIs for the genetic models. A total of 1097 identified results, along with 36 qualified studies were included: for MTHFR C677T polymorphism, a total of 36 studies was comprised of 11,261 cases and 13,318 controls and for MTHFR A1298C polymorphism, a number of 19 studies contained 7424 cases and 8204 controls. Likewise, for C677T polymorphism, an increased risk of BC was seen for the allelic (OR 1.21, 95% CI 1.09-1.33, P < 0.01, I2 = 78.9%), dominant (OR 1.17, 95% CI 1.05-1.30, P < 0.01, I2 = 71.8%), recessive (OR 1.43, 95% CI 1.23-1.67, P < 0.01, I2 = 55.8%), and homozygous models (OR 1.48, 95% CI 1.25-1.75, P < 0.01, I2 59.9%) among BC patients compared to controls. Also, in terms of A1298C polymorphism, an association was found between the allelic (OR 1.15, 95% CI 1.04-1.28, P < 0.01, I2 70.4%) and homozygous models (OR 1.38, 95% CI 1.15-1.66, P < 0.01, I2 44.2%) with the risk of BC. In conclusion, findings revealed that MTHFR C677T variant might be a factor that predisposes BC in Asians. Furthermore, it was found that A1298C variant acts as a BC risk factor, particularly in a Western Asia population.