Methylenetetrahydrofolate Reductase Gene A1298C Research Articles

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.

Associations of serum 25-hydroxyvitamin D with serum folate, cobalanin, and homocysteine concentrations and methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in healthy adults.

The aim of this study was to investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] with various demographic, anthropometric, and genetic characteristics and biochemical parameters in healthy Greek adults. Demographic (age and sex), anthropometric (body mass index/BMI), and genetic (MTHFR gene polymorphisms) characteristics and biochemical parameters (serum folate, cobalamin/Cbl, and total homocysteine/tHcy concentrations), which had been recorded and measured, among others, in the framework of periodic medical examination (military personnel) or check-up (non-military personnel) of 383 healthy Greek adults (199 men and 184 women) were analyzed. Serum 25(OH)D, tHcy, folate, and Cbl levels were determined using immunoassay methods. The MTHFR C677T and A1298C gene polymorphisms were genotyped using polymerase chain reaction and reverse hybridization. Serum 25(OH)D concentrations were correlated with Cbl levels and MTHFR C677T gene polymorphism, while they had a reverse correlation with serum tHcy levels, age, and BMI. There was no significant correlation between serum 25(OH)D concentrations and sex, serum folate levels, and smoking status. Individuals with the 677TT genotype had statistically significantly lower serum 25(OH)D levels than those with the 677CC or 677CT genotype, while individuals with the 1298CC genotype had statistically significantly higher serum 25(OH)D levels than those with 1298AA or 1298AC genotype. Moreover, the reverse correlation between the serum 25(OH)D and tHcy levels was statistically significant in all six MTHFR genotypes. Serum 25(OH)D levels are associated with age, BMI, serum tHcy, and Cbl levels and MTHFR C677T gene polymorphism. The most significant finding of our study is the observed reverse correlation of serum 25(OH)D levels with serum tHcy levels. Considering that vitamin D deficiency and hyperhomocysteinemia (HHcy) are associated with an increased risk for cardiovascular diseases (CVDs), we suggest that individuals with high serum tHcy levels should be further investigated for, inter alia, their serum 25(OH)D levels.

INFLUENCE OF THE METHYLENE TETRAHYDROFOLATE REDUCTASE (MTHFR) GENE POLYMORPHISMS ON SERUM FOLATE, COBALANIN AND HOMOCYSTEINE LEVELS IN HEALTHY GREEK ADULTS

Objective: Methylene tetrahydrofolate reductase (MTHFR) is a key enzyme of homocysteine metabolism participating in the folate cycle. It is well known that hyperhomocysteinemia is associated with an increased risk for cardiovascular disease. The aim of this study was to investigate the association of MTHFR C677T and MTHFR A1298C gene polymorphisms with serum folate, cobalamin (Cbl) and homocysteine (Hcy) concentrations in healthy Greek adults. Design and method: The MTHFR C677T and A1298C gene polymorphisms were genotyped in 383 healthy Greek adults (199 men; mean age±SD: 37.3±8.2 years) using polymerase chain reaction and reverse hybridization. Serum folate, Cbl and total Hcy (tHcy) levels were determined using immunoassays methods. Results: Among the 383 individuals, 73 (19.1%) were normal (CC), 202 (52.7%) were heterozygous (CT) and 108 (28.2%) were homozygous (TT) regarding the MTHFR C677T gene polymorphism, while 263 (68.7%) were normal (AA), 105 (27.4%) were heterozygous (AC) and 15 (3.9%) were homozygous (CC) regarding the MTHFR A1298C gene polymorphism. The overall C and T allele frequency for the MTHFR C677T gene polymorphism was 45.4% and 54.6%, respectively, while the overall A and C allele frequency for the MTHFR A1298C gene polymorphism was 82.3% and 17.6%, respectively. The individuals with 677TT genotype had significantly lower serum folate and significantly higher serum tHcy levels than individuals with 677 CC or CT genotypes. On the contrary, the A1298C gene polymorphism had no significantly influence on serum folate and tHcy levels. Conclusions: Serum folate and tHcy levels are influenced by the existence of the MTHFR C677T gene polymorphism (mainly 677TT genotype). Individuals with low serum folate levels and/or high serum tHcy levels should be further investigated for a possible existence of MTHFR C677T and not A1298C gene polymorphisms, with aim to determine the suitable treatment.

Effect of MTHFR A1298C Gene Polymorphism on Acute Coronary Syndrome.

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Acute coronary syndrome is a manifestation of CVD. In Indonesia, limited studies have been conducted on genetics as a potential risk factor for acute coronary syndrome (ACS). Consequently, this study aimed to examine the effect of the methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism on the incidence of ACS. The study employed a case-control design. Outpatients from the cardiology and internal medicine clinics at the University of Airlangga (UNAIR) Hospital in Surabaya, Indonesia, constituted the study population. The case group comprised 60 patients with a history of ACS, while the control group consisted of 30 patients without a history of cardiovascular complaints. MTHFR A12980C gene polymorphism examination was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR RFLP) method at the Tropical Disease Center UNAIR Laboratory. Among the ACS group, 29 (48.1%), 13 (21.7%), and 18 (30%) of the individuals had AA, AC, and CC genotype patterns, respectively. In the control group, 16 individuals had AA (53.3%), 6 AC (20%), and 8 CC (26.7%). The C allele variant was identified in 41% of the ACS group and 37% of the control group. The odds ratio (OR) for the incidence of ACS was 1.195 (95% confidence interval [CI]; 0.381-3.752), 1.241 (95% CI; 0.481-3.486), and 1.222 (95% CI; 0.381-3.752). Chi-square analysis revealed no association between MTHFR A1298C gene polymorphism and the incidence of ACS (P > 0.05). MTHFR A1298C gene polymorphism did not significantly affect ACS incidence.

Association of methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms with serum folate, cobalanin and homocysteine concentrations in Greek adults

Methylene tetrahydrofolate reductase (MTHFR) is a key enzyme of homocysteine metabolism participating in the folate cycle. The aim of this study was to investigate the association of MTHFR C677T and MTHFR A1298C gene polymorphisms with serum folate, cobalamin (Cbl) and homocysteine (Hcy) concentrations in healthy Greek adults. The MTHFR C677T and A1298C gene polymorphisms were genotyped in 383 healthy Greek adults (199 men and 184 women) using polymerase chain reaction and reverse hybridization. Serum folate, Cbl and total Hcy (tHcy) levels were determined using immunoassays methods. Among the 383 individuals, 73 (19.1%) were normal (CC), 202 (52.7%) were heterozygous (CT) and 108 (28.2%) were homozygous (TT) regarding the MTHFR C677T gene polymorphism, while 263 (68.7%) were normal (AA), 105 (27.4%) were heterozygous (AC) and 15 (3.9%) were homozygous (CC) regarding the MTHFR A1298C gene polymorphism. The overall C and T allele frequency for the MTHFR C677T gene polymorphism was 45.4% and 54.6%, respectively, while the overall A and C allele frequency for the MTHFR A1298C gene polymorphism was 82.3% and 17.6%, respectively. The MTHFR C677T and not the A1298C gene polymorphism had a significantly influence on serum folate and tHcy levels. The individuals with 677TT genotype had significantly lower serum folate and significantly higher serum tHcy levels than individuals with 677 CC or CT genotypes. Serum folate and tHcy levels are influenced by the existence of the MTHFR C677T gene polymorphism (mainly 677TT genotype). Individuals with low serum folate levels and/or high serum tHcy levels should be further investigated for a possible existence of MTHFR C677T and not A1298C gene polymorphisms, with aim to determine the suitable treatment.

The role of methylenetetrahydrofolate reductase gene polymorphisms hypercoagulable status of coronavirus disease

Abstract Background: Hypercoagulation is a hallmark in coronavirus disease (COVID-19). The activity of the enzyme methylenetetrahydrofolate reductase (MTHFR) determines homocysteine levels, and polymorphisms in the enzyme’s gene can influence the enzyme activity with a consequence of hypercoagulability in patients with COVID-19. Objectives: To investigate the association of two single nucleotide polymorphisms (SNPs) in the MTHFR gene with hypercoagulability status in COVID-19. Materials and Methods: This is a retrospective cross-sectional study, which included 90 patients diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with variable severity. Patients were classified according to D-dimer level at admission into two groups: with and without hypercoagulability. Nucleic DNA was extracted from leukocytes and gene fragments corresponding to C677T and A1298C MTHFR gene were amplified and genotyped using allele specific polymerase chain reaction. Results: Hypercoagulation was reported in 42.22% of the patients. The mutant homozygous genotype (TT) was more frequent among hyper - than normocoagulable patients (13.6% vs. 1.92%) with a significant difference (odds ratio [OR] = 9.28, 95% confidence interval [CI] = 1.02–84.78, P = 0.048). Furthermore, T allele was more common among hyper- than normocoagulable patients (28.95% vs. 13.46%) with a significant difference (OR = 2.62, 95% CI = 1.24–5.5, P = 0.012). In contrast, the SNP A1298C had no significant impact. Conclusions: The TT genotype and T allele of C677T polymorphism but not A1298C in cMTHFE gene could be considered a risk factor for the hypercoagulable status in COVID-19.

Relationship between methylenetetrahydrofolate reductase gene polymorphisms and methotrexate drug metabolism and toxicity.

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, and methotrexate (MTX) is the key drug for ALL. Studies on the relationship between High-Dose methotrexate (HD-MTX) toxicity and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C genes have drawn different conclusions. This study aimed to investigate the relationship between the polymorphism of MTHFR C677T and A1298C genes and the toxicity responses of MTX. The MTHFR C677T and A1298C genotypes of 271 children with ALL who received HD-MTX chemotherapy in southern China from September 2017 to June 2021 were analyzed, and the toxicity of HD-MTX was evaluated and analyzed according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0. The MTHFR C677T and A1298C gene polymorphisms were not correlated with the 48-hour MTX blood concentrations (P>0.05). Unconditional logistic regression model analysis also revealed that the risk of liver function impairment [odds ratio (OR) =1.656, 95% confidence interval (CI): 1.179-2.324, P<0.05] and mucosal damage (OR =1.508, 95% CI: 1.042-2.183, P<0.05) were 1.656 and 1.508 times higher for the heterozygous mutant (CT), and homozygous mutant (TT) mutant type than for the wild-type (CC), wild-type, respectively. The risk of neutropenia and liver function impairment were 0.498 (OR =0.498, 95% CI: 0.251-0.989, P<0.05) and 6.067 (OR =6.067, 95% CI: 1.183-31.102, P<0.05) times higher in low-risk children with CT+TT mutant genotypes than in those with CC wild genotypes, respectively. Furthermore, the risk of mucosal damage was 1.906 times higher in high-risk children with the CT+TT genotype than in those with the CC genotype (OR =1.906, 95% CI: 1.033-3.518, P<0.05). The MTHFR A1298C genotypes differed in the incidence of liver function damage and gastrointestinal toxic reactions in children with ALL. Nonetheless, no increased risk of liver function impairment nor gastrointestinal reactions in children with the heterozygous mutant (AC)+CC mutation was observed. Advancements in MTHFR genotype testing in children with ALL and the introduction of personalised treatments based on genotype results during HD-MTX chemotherapy will help to predict, prevent, and reduce the occurrence of adverse MTX-related toxic reactions.

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.

P-43 C677T and A1298C MTHFR gene polymorphisms and response to fluoropyrimidine-based chemotherapy in mestizo patients with metastatic colorectal cancer

The objective of this study was to assess the association between C677T and A1298 methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms (SNPs) and response to first-line fluoropyrimidine-based chemotherapy for metastatic colorectal adenocarcinoma.

C677T and A1298C MTHFR gene polymorphisms and response to fluoropyrimidine-based chemotherapy in Mestizo patients with metastatic colorectal cancer.

To assess the association between C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs) and response to first-line fluoropyrimidine-based chemotherapy for metastatic colorectal adenocarcinoma. A total of 68 patients were prospectively followed up in San Juan de Dios Hospital (San José, Costa Rica) from January 2019 to November 2020. Patients received first-line therapy with capecitabine or 5-fluorouracil in combination with oxaliplatin or irinotecan. Germline and somatic DNA was extracted from blood samples and paraffin-embedded tissue, respectively. Overall response rate (partial response + complete response) was assessed according to RECIST 1.1 criteria. Cox regression models were performed to identify the effect of MTHFR C677T and A1298C SNPs on progression-free survival (PFS) and overall survival (OS) (NCT registration number: 03852290). Patients harboring one or both T alleles of the MTHFR C677T SNP had better overall response than homozygous wild-type individuals [odds ratio (OR): 3.21; 95% confidence interval (CI), 1.05-9.81; P = 0.03]. No association was found between the MTHFR A1298C genotypes and overall response (OR: 0.75; 95% CI, 0.26-2.20; P = 0.60). Patients with the MTHFR 677 TT and CT genotypes had longer PFS than CC individuals (hazard ratio: 0.53; 95% CI, 0.28-0.98; P = 0.045), even after adjustment for confounders (hazard ratio: 0.50; 95% CI, 0.25-0.98; P = 0.04). We found no association between the MTHFR A1298C SNP and PFS (hazard ratio: 1.35; 95% CI, 0.72-2.55; P = 0.34). None of the SNPs was associated with OS. Patients carrying at least one mutant allele of the MTHFR C677T SNP had a better overall response and longer PFS than wild-type homozygous patients.

Association of Methylene Tetrahydrofolate Reductase Gene A1298C (Rs1801131) Polymorphism with Myocardial Infarction among Sudanese Patients

Background: Myocardial infarction (MI) is among the leading causes of mortality worldwide. Variations in folate metabolism including genetic polymorphisms in the key metabolic enzymes had showed influences in the MI process. Objectives: To determine whether the C1298A transition in the Methylene Tetrahydrofolate Reductase ( MTHFR ) gene is associated with increased risk for MI among Sudanese patients. Material and methods: This is a hospital based case control study in which a total of 140 Sudanese subjects were enrolled, 70 patients with myocardial infarction and 70 age- and sex matched healthy volunteers as a control group. Genomic DNA was extracted by (QIA gene, Korea) kits and the SNPs genotypes were determined using polymerase chain reaction followed by restriction fragment length polymorphism (PCR- RFLP). Data of this study were collected using a structured interview questionnaire and analyzed by statistical package for social sciences (version 21). Results: The frequency of the AA genotype was higher in the patients group compared with control (96%, 71% respectively); while the AC genotype was higher in the control (20%, 5% respectively), while the CC genotype was not observed in this study population. The frequencies of A and C alleles were 0.68 and 0.02 respectively in MI patients while frequencies were 0.60 and 0.10 respectively in the control group. No statistically significant association was observed between MTHFR genotypes and MI (P. values = 0.4 and 0.1 for AA and AC genotypes respectively). Conclusion: In this study population, the A1298C MTHFR polymorphism is not associated with the risk of MI among the Sudanese population.

Study of A1298C MTHFR Gene Polymorphism as a Risk Factor for Neural Tube Defects in the Eastern Algerian Population

Background: As C677T mutation, A1298C mutation in methylene tetrahydrofolate reductase (MTHFR) gene results in a decreased MTHFR activity but to a less extent, it is known as a risk factor of predisposition to human neural tube defects (NTDs), in some populations. Our objective was therefore to study, for the first time in Algerian population, if A1298C polymorphism confers risk for the occurrence of this abnormality. We have examined the distribution of the genotype and the allele frequencies of A1298C mutation, and also their influence on plasma homocysteine (Hcy) concentration. Patients and Methods: We studied this polymorphism in 38 mothers of NTD cases and 67 control individuals of an eastern Algerian population. The mutation was determined by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR/RFLP). Plasma homocysteine concentration was analyzed using an automated chemiluminescence method. Results: No signi?cant association could be observed between allele and genotypes frequencies of A1298C MTHFR gene polymorphism and NTDs risk. However, we could observe that A1298C polymorphism affects homocysteine metabolism in mothers of NTD cases leading to homocysteine concentration values higher in AA genotype and lower in AC/CC genotypes (15.29 ± 11.8 μmol/l vs. 8.63 ± 3.83 μmol/l, p Conclusion: Data indicate that A1298C MTHFR gene polymorphism might be a risk factor by affecting homocysteine metabolism in mothers of Algerian children with NTDs.

The association of methylene tetrahydrofolate reductase (MTHFR) A1298C gene polymorphism, homocysteine, vitamin B12, and folate with coronary artery disease (CAD) in the north of Iran

Abstract Background We pursued to find out the possible association of Methylene tetrahydrofolate reductase (MTHFR) A1298C gene polymorphism, blood homocysteine, vitamin B12, and folate with Coronary artery disease (CAD) in the study population in Guilan, north of Iran. Material and Methods Ninety patients with CAD and 76 healthy controls were evaluated. MTHFR A1298C polymorphism and its genotype frequency, the plasma level of homocysteine, vitamin B12 and folate were evaluated by using ARMS-PCR, ELISA, and Chemiluminescence methods, respectively. Results The frequency of genotypes, A, AC and CC in CAD were 40, 35.6, 24.4%, respectively which was significantly different (p=0.016) from the control group that were 26.3, 57.9 and 15.8%, respectively. The serum level of vitamin B12 and folate in genotype A1298C were not statistically significant between two groups (p&gt;0.05), however, the plasma homocysteine in patients with CAD was remarkably higher than the control group (p&lt;0.001). Additionally, in CAD patients the plasma level of homocysteine in the AC genotype was significantly higher than the control subjects (p=0.005). Conclusion It is thus concluded that MTHFR A1298C gene polymorphism is associated with CAD. It seems that the AC genotype of MTHFR A1298C polymorphism might have a protective effect on CAD.

Methylenetetrahydrofolate reductase gene polymorphisms in the risk of polycystic ovary syndrome and ovarian cancer.

Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) in hormone metabolism pathways might cause metabolic disturbances and contribute to the development of polycystic ovary syndrome (PCOS) and ovarian cancer, but the published studies were inconsistent. The aim of the present study was to evaluate the MTHFR C677T (rs1801133) and A1298C (rs1801131) gene polymorphisms in the risk of PCOS and ovarian cancer by meta-analysis. A comprehensive electronic search was conducted in databases for studies published from 1995 to 2020. The pooled ORs were calculated by Revman 5.2 software. Twenty-nine articles including 45 case–control studies were included. We found that MTHFR C677T polymorphisms were correlated with elevated PCOS risk (TT vs. CT+CC: OR = 1.41, 95%CI = 1.20–1.67; TT+CT vs. CC: OR = 1.54, 95%CI = 1.07–2.22; CT vs. CC+TT: OR = 1.18, 95%CI 1.04–1.33; TT vs. CC: OR = 1.47, 95%CI = 1.03–2.11; T vs. C: OR = 1.25, 95%CI = 1.06–1.47), which were more obvious in Middle Eastern subgroup. MTHFR A1298C polymorphisms were also associated with overall PCOS susceptibility (CC vs. AC+AA: OR = 2.55, 95% CI = 1.61–4.03; CC+AC vs. AA: OR = 1.84, 95%CI = 1.04–3.28; CC vs. AA: OR = 2.66, 95%CI = 1.68–4.22; C vs. A: OR = 1.67, 95%CI = 1.03–2.71), which were mainly reflected in Asian subjects. For ovarian cancer, MTHFR C677T polymorphisms were only related with elevated ovarian cancer risk in Asian population, while no significant association was found for A1298C polymorphisms. This meta-analysis suggested that MTHFR C677T and MTHFR A1298C polymorphisms were correlated with elevated PCOS risk. MTHFR C667T only posed a higher risk for ovarian cancer in Asians instead of other populations, while MTHFR A1298C polymorphisms were not related to ovarian cancer risk. Further studies are needed to validate the conclusion.

MTHFR gene polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis based on 16 studies.

Rheumatoid arthritis (RA) is the most common autoimmune rheumatic disease, in which an epigenetic implication in the disease etiopathogenesis has been noted. Here in this meta-analysis, we attempted to investigate the pooled association of methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms and susceptibility to RA risk. A systematic search was performed in the main databases, including MEDLINE and Scopus to search for studies assessing the association between MTHFR gene C677T and A1298C polymorphisms and the risk of RA prior to December 2019. In this meta-analysis, 15 studies with 2165 patients and 1751 healthy controls for C677T SNP and 14 studies containing 2021 patients and 1760 healthy controls for A1298C SNP were included. A significant positive association between C677T SNP and RA risk was recognized in the dominant, recessive, and allelic model, but not TT and CT genotypes. The results indicated that the risk of RA in African population was increased under all genotype models while these results were repeated in Asian population just for recessive model, allelic model, and TT genotype. Moreover, the analysis of A1298C SNP demonstrated a significant association in overall population according to only the recessive model and CC genotype. Subgroup analysis according to the genotyping method indicated that RFLP-PCR method could impress the results of association between MTHFR gene A1298C and C677T SNPs and RA risk. The outcome of this meta-analysis indicated that MTHFR gene C677T SNP was much possibly be associated with RA risk.

Association between A1298C and C677T methylenetetrahydrofolate reductase gene polymorphisms and the risk of acute lymphoid and myeloid leukemia

Background: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate metabolism, DNA methylation and synthesis. Two MTHFR polymorphisms, C677T and A1298C, have been associated with reduced enzyme activity. Rapidly replicating cell types, such as hematopoietic cells, may be especially sensitive to changes in the availability of intracellular folate. The aim of this case-control study was to evaluate whether the mentioned polymorphisms in MTHFR gene plays a role in altering susceptibility to acute myeloid leukemia and acute lymphoblastic leukemia. Material and methods: 281 patients comprising 101 patients with acute lymphoblastic leukemia and 180 patients with acute myeloid leukemia as well as 490 normal individuals as control group were studied for the C677T and the A1298C MTHFR gene polymorphisms using PCR. The PCR products were digested with HinfI and Mbo‌‌‌‌‌II restriction enzymes respectively (RFLP). The results were electrophoresed on agaros gel and analyzed using SPSS software. Results: The number of patients with acute lymphoblastic leukemia who had C677T polymorphism was less than the control group, but this difference was not significant. Also, combination of C677T/A1298C genotypes in both case and control groups, showed no increase of susceptibility to acute myeloid leukemia and/or acute lymphoblastic leukemia risk. There was no significant relationship between common MTHFR variants and the risk of acute myeloid leukemia and acute lymphoblastic leukemia in controls and the cases. Conclusion: Our findings showed that the MTHFR C677T and A1298C gene variants do not have a major influence on the susceptibility to acute lymphoblastic leukemia and acute myeloid leukemia in Iranian individuals. However, the C677T polymorphism has a protection role in acute lymphoblastic leukemia group, but this difference was not statistically significant.

Association of Intake Folate and Related Gene Polymorphisms with Breast Cancer.

Breast cancer is one of the most common malignancies in women worldwide and is associated with a variety of risk factors. Folate and vitamin B12 are key elements of the one-carbon metabolism pathway where methylenetetrahydrofolate reductase (MTHFR) plays a significant role. Though many molecular and epidemiological studies have been performed to explore the relationship between intake folate, vitamin B12, MTHFR gene polymorphism and breast cancer risk, there is no consensus to date. By reviewing the relevant literatures and summarizing the potential effect of dietary folate intake on MTHFR genes polymorphism and breast cancer risk, we conclude that MTHFR C677T gene polymorphism is associated with breast cancer risk among Asian, but not Caucasians, and the MTHFR A1298C gene polymorphism is not a susceptibility factor of breast cancers. Concomitant low activity of MTHFR enzyme resulted from C677T gene polymorphism and low dietary folate intake is associated with increased breast cancer risk.

Methylene tetrahydrofolate reductase gene mutation in sickle cell anaemia patients in Lagos, Nigeria.

IntroductionThe significant causes of mortality among individuals with sickle cell anaemia (SCA) such as acute chest syndrome and cerebrovascular disease are related to vascular occlusion. Polymorphisms of the methylene tetrahydrofolate reductase (MTHFR) gene in persons with sickle cell anaemia have been suggested as a potential risk for vaso-occlusive events, with the C677T and A1298C polymorphisms being the commonest. This study therefore aimed to establish the pattern of MTHFR C677T and A1298C gene mutations among adults with HbSS phenotype attending the Haematology Clinic in Lagos State University Teaching Hospital Lagos, Nigeria.MethodsA cross-sectional study was done among SCA patients attending the Haematology Clinic of the Lagos State University Teaching Hospital (LASUTH), using age and sex matched HbAA controls. DNA extraction and gene analysis were done. The selective amplification of a particular segment of the DNA by polymerase chain reaction (PCR) was done and subsequent digestion of the amplified MTHFR gene into its various fragments.ResultsThe overall prevalence of the C677T mutation among participants was 19.3% (37 of 192), while the prevalence of A1298C was 15% (29 of 192).ConclusionThe prevalence of MTHFR C677T was higher than A1298C mutations among sickle cell anaemia subjects.

P3132Methylenetetrahydrofolate reductase A1298C as a risk factor for rheumatic heart disease in indonesian population

Abstract Introduction Rheumatic heart disease (RHD) is a chronic condition causing damage in cardiac valvular tissues due to acute rheumatic fever (ARF) post Streptococcus pyogenes or Group A β hemolytic Streptococcus (GABHS) infection. The damage to the valve tissue within the heart can lead to congestive heart failure, strokes, endocarditis, and death. However, only 3–6% of post-streptococcal infection individuals develop ARF, suggesting host susceptibility in the pathogenesis of ARF. Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) may be linked to the genetic susceptibility of the host that results in abnormal autoimmune response to the infection. Purpose This study aims to look at MTHFR A1298C polymorphism as a risk factor for rheumatic heart disease in Indonesian population. Methods This was an observational analytical study with case control approach. Blood samples were obtained from 36 Indonesian RHD patients with confirmed diagnosis of RHD using echocardiography and 36 healthy controls. Patients DNA were isolated and then amplified using polymerase chain reaction followed by restriction fragment length polymorphism analysis using MboII restriction enzyme. Results We observed a significant difference between genotypic distribution between cases and controls (OR = 4.6, 95% CI = 1.697–12.469, p=0.002). The genotype frequency of MTHFR A1298C AA (wild type) was 36.1%, heterozygous AC was 47.2%, and 16.7% of CC in the cases group. In the control group, the genotype frequency of the wild type AA was 72.2%, AC was 27.8%, and homozygous CC was 2.8%. Conclusion Compared with the CC frequency in the control population, the frequency of MTHFR CC was 5 times higher in individuals with rheumatic heart disease (p=0.002), suggesting that MTHFR A1298C gene variant may contribute to the pathogenesis of RHD. Individuals with MTHFR 1298C have a risk of 4.6 times higher to develop ARF post streptococcal infection.

The relationship between MTHFR polymorphisms and abortion in Iranian women

BackgroundRecurrent spontaneous abortion (RSA) is a significant obstetrical complication during pregnancy. Two common polymorphisms (C677T and A1298C) of the methylenetetrahydrofolate reductase (MTHFR) gene are risk factors for RSA. This study was performed to determine the effect of C677T and A1298C polymorphisms in RSA. The true relationship between these two mutations and risk of recurrent spontaneous abortion is unknown, and it is unclear if women with these mutations should be given anticoagulants during pregnancy. Materials and methodsIn this prospective and experimental study, one hundred and fifty three individuals were referred with clinical findings that included recurrent spontaneous abortions minimum of 2 and maximum of 5. Total genomic DNA was isolated from peripheral blood samples. To determine the frequency of the two common C677T and A1298C MTHFR gene polymorphisms in the patients, we used PCR-restriction fragment length polymorphism method. ResultsThe frequency of Heterozygous and homozygous C677T polymorphisms were 18.13% and 13.1% respectively. The frequency of Heterozygous and homozygous A1298C polymorphisms were 18.3% and 15.7% respectively. The frequency of Heterozygous C677T and A1298C polymorphisms were 26.8% and wild-type individuals were 7.8%. All female subjects who had heterozygous or homozygous C677T and A1298C polymorphisms with recurrent RSA were followed and those who received appropriate anti-coagulant therapy resulted in successful pregnancy. ConclusionIn present study, we provided witness to support the relationship between MTHFR C677T and A1298C polymorphisms and recurrent spontaneous abortion. Also, we suggest that anticoagulation therapy of these patients during pregnancy could lead to a successful pregnancy outcome.