MTRR A66G Polymorphisms Research Articles

Interrelationships among MTHFR gene polymorphisms, MTRR gene polymorphisms, and HBV gene BCP 1762/1764 mutations with disease progression in Chronic hepatitis B virus infection patients

Objective Chronic hepatitis B virus (HBV) infection is a major disease that seriously affects the health of patients. In this paper, the relationship among MTHFR gene polymorphism, MTRR gene polymorphism and 1762/1764 mutation in the BCP region of HBV gene with disease progression in chronic HBV patients was studied. Methods A total of 144 chronic HBV infection patients from January 2021 to June 2022 in the Third People’s Hospital of Zigong City, were included as the study subjects. These patients were divided into hepatitis B primary liver cancer patients group (PLC) in 51 cases, Non-primary liver cancer patients group (Non-PLC) in 93 cases, Non-PLC is also divided into chronic hepatitis B virus carriers (CHC) in 49 cases, hepatitis B Live cirrhosis(LC) in 44 cases. MTHFR (C677T), MTRR (A66G) and MTHFR (A1298C) genes polymorphisms were detected by PCR-dissolution curve. The level of HBV-DNA was quantified by real-time PCR, and the 1762/1764 mutation site in the BCP region of the HBV gene were detected by ARMS-PCR. Data were statistically analyzed using the SPSS statistical software. Results The proportion of HBV mutations in BCP region 1762/1764 in PLC group was 82.4%, which was higher than that in LC group (63.6%) and CHC group (51.0%), and the differences were statistically significant (p < 0.05). There were no significant differences in the distribution of MTHFR C677T, MTHFR A1298C and MTRR A66G polymorphisms among CHC, LC and PLC (p > 0.05). The polymorphism distribution of MTHFR C677T, MTRR A66G and MTHFR A1298C genes in patients with chronic hepatitis B virus infection at different stages (CHC, LC and PLC) showed no gender or age differences between and within groups (p > 0.05). Among the patients with MTHFR 677CT + TT, MTRR 66AG + GG and MTHFR 1298AA genotype, the proportion of HBV mutation in BCP region 1762/1764 in PLC group was higher than that in CHC group and LC group, and the differences were statistically significant (p < 0.05). Folate levels in the PLC group were lower than those in the non-PLC group (CHC and LC patients), and the difference was statistically significant compared with the CHC group (p < 0.05). In different MTHFR C677T and MTRR A66G genotypes, the serum GGT activity were statistically significant between mutant PLC and mutant Non-PLC (p < 0.05). Conclusion MTHFR C677T, MTRR A66G and MTHFR A1298C gene polymorphisms distribution have no gender and age differences in chronic hepatitis B virus infection patients. The mutation of HBV gene BCP region 1762/1764 may be associated with the occurrence and development of liver cancer in patients with chronic HBV infection. Single difference of MTHFR C677T, MTHFR A1298C and MTRR A66G gene polymorphisms may have little effect on the disease progression in patients with chronic HBV infection. MTHFR 677CT + TT, MTRR 66AG + GG and MTHFR 1298AA genotype combined with HBV gene BCP region 1762/1764 mutation may be closely related to the occurrence and development of hepatitis B liver cancer.

Association of MTHFR C677T, MTHFRA1298C, and MTRRA66G Gene Polymorphisms with Hyperhomocysteinemia and Its Modulation by the Combined Effect of Vitamin B12 and Folate in Chinese Population with Hypertension

BackgroundIn China, the MTHFR 677T allele, unlike in most Western populations, is a rare genetic variant linked to various disorders. The contributing nutritional and genetic factors to this genetic risk remain unclear. ObjectiveThis study aimed to elucidate the interactions between genetic variations in total homocysteine (tHcy) pathway genes, serum tHcy concentrations, and nutritional factors in a Chinese population with hypertension. MethodsThis study analyzed 1304 Chinese adults with hypertension aged ≥18 y enrolled in the China Precision Nutrition and Health KAP Real World Study (CPNAS). Serum concentrations of vitamin B12 and folate were measured using the magnetic microparticle chemiluminescence method, and tHcy concentrations were measured using Hcy Assay kits. Identification of the MTHFR C677T, MTHFR A1298C, and MTRR A66G polymorphisms was performed via time-of-flight nucleic spectrometry. ResultsOur findings revealed significant sex differences in tHcy concentrations, with males exhibiting higher tHcy concentrations than females (13.95 μmol/L vs. 11.15 μmol/L, P < 0.001). Individuals deficient in both vitamin B12 and folate had an increased risk of hyperhomocysteinemia (H-Hcy) (57.4%). In contrast, the prevalence of H-Hcy was lower among those deficient in either vitamin B12 (31.1%) or folate (23.2%) alone. Significant associations were identified between the MTHFR C677T and A1298C polymorphisms and elevated serum tHcy concentrations, particularly in individuals homozygous for the T allele. Conversely, the MTRR A66G genotype did not show a significant correlation with tHcy concentrations. Optimal vitamin B12 concentrations significantly modulated the genotypic effect on tHcy concentrations, with individuals having adequate vitamin B12 and folate exhibiting low tHcy concentrations, even among high-risk genotypes (TT). ConclusionsAdequate concentrations of folate and vitamin B12 significantly reduce serum tHcy concentrations and mitigate the genotypic impact on tHcy concentrations, highlighting the potential for targeted nutritional interventions to manage cardiovascular risks associated with H-Hcy.This trial was registered at clinicaltrials.gov as ChiCTR2100051983.

Docosahexaenoic acid, eicosapentaenoic acid, arachidonic acid, and neural tube defects in Tunisian population.

To determine the effect of maternal status in (plasma and red blood cell) folate, vitamin B12, homocysteine, and vitamin D, as well as their interaction with MTHFR (C677T and A1298C) and MTRR A66G polymorphisms, on maternal plasma docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) levels and the risk of neural tube defects (NTDs). ARA, EPA, and DHA composition was assessed using capillary gas chromatography. ARA and DHA levels were higher in controls than in case mothers for low plasma folate status. For low red blood cell folate status, DHA levels were higher in controls than in case mothers. For high homocysteine levels, ARA and DHA levels were higher in controls than in case mothers. NTD mothers had lower EPA and DHA levels for low vitamin B12 levels. NTD mothers had lower DHA levels for low vitamin D levels. For low plasma folate status, DHA levels in the MTHFR C677T gene and ARA and EPA levels in MTHFR A1298C gene were different among the three genotypes in case mothers. DHA levels in the MTHFR C677T gene were different among the three genotypes in case mothers for both low and high homocysteine levels. For low vitamin B12 levels, ARA and DHA levels were different among the three genotypes of the MTHFR C677T gene in case mothers. In the MTHFR C677T gene, ARA and DHA levels were different among the three genotypes in case mothers for low vitamin D levels. More advanced research is required to verify a suitable biochemical parameter status in relation to the genotypes in pregnant women.

Association of MTHFR (C677T, A1298C) and MTRR A66G polymorphisms with fatty acids profile and risk of neural tube defects.

This study aims to determine if 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and methionine synthase reductase (MTRR A66G) gene polymorphisms were associated with fatty acid (FA) levels in mothers of fetuses with neural tube defects (NTDs) and whether these associations were modified by environmental factors. Plasma FA composition was assessed using capillary gas chromatography. Concentrations of studied FA were compared between 42 mothers of NTDs fetuses and 30 controls as a function of each polymorphism by the Kruskal-Wallis nonparametric test. In MTHFR gene C677T polymorphism, cases with (CT + TT) genotype had lower monounsaturated FAs (MUFA) and omega-3 polyunsaturated FA (n-3 PUFA) levels, but higher omega-6 polyunsaturated FAs (n-6 PUFA) and omega-6 polyunsaturated FAs: omega-3 polyunsaturated FAs (n-6:n-3) ratio levels. In MTRR gene A66G polymorphism, cases with (AG + GG) genotype had lower MUFA levels, but higher PUFA and n-6 PUFA levels. Controls with (AG + GG) genotype had lower n-6 PUFA levels. In MTHFR gene C677T polymorphism, cases with smoking spouses and (CT + TT) genotype had lower MUFA and n-3 PUFA levels, but higher PUFA, n-6 PUFA, and n-6:n-3 ratio levels. Cases with (CT + TT) genotype and who used sauna during pregnancy had lower n-3 PUFA levels. In MTRR gene A66G polymorphism, cases with (AG + GG) genotype and who used sauna during pregnancy had higher PUFA and n-6 PUFA levels. Further research is required to clarify the association of FA metabolism and (MTHFR, MTRR) polymorphisms with NTDs.

Global DNA Methylation Levels Viz-a-Viz Genetic and Biochemical Variations in One Carbon Metabolic Pathway: An Exploratory Study from North India.

Despite the importance of one carbon metabolic pathway (OCMP) in modulating the DNA methylation process, only a few population-based studies have explored their relationship among healthy individuals. This study aimed to understand the variations in global DNA methylation levels with respect to selected genetic (CBS 844ins68, MTRR A66G, MTR A2756G, and MTHFR C677T polymorphisms) and biochemical (folate, vitamin B12, and homocysteine) markers associated with OCMP among healthy North Indian adults. The study has been conducted among 1095 individuals of either sex (69.5% females), aged 30-75 years. A sample of 5 mL of blood was collected from each participant. Homocysteine, folate, and vitamin B12 levels were determined using the chemiluminescence technique. Restriction digestion was performed for genotyping MTRR A66G, MTR A2756G, and MTHFR C677T polymorphisms and allele-specific PCR amplification for CBS 844ins68 polymorphism. Global DNA methylation levels were analyzed using ELISA-based colorimetric technique. Of the selected genetic and biochemical markers, the mutant MTRR A66G allele was positively associated with global DNA methylation levels. Further, advanced age was inversely associated with methylation levels. MTRR 66GG genotype group was hypermethylated than other genotypes in folate replete and vitamin B12 deficient group (a condition prevalent among vegetarians), suggesting that the G allele may be more efficient than the wild-type allele in such conditions. Global DNA methylation levels appeared to be more influenced by genetic than biochemical factors. MTRR 66G allele may have a selective advantage in vitamin B12 deficient conditions. Further research should be undertaken to understand how genetics affects epigenetic processes.

Association of methionine synthase reductase (MTRR A66G) polymorphism with susceptibility to acute lymphoblastic leukemia

Background and Objectives. The enzyme methionine synthase reductase is involved in cellular methylation reactions, DNA synthesis, and epigenetic processes. It is encoded by the MTRR gene, which garnered a lot of attention in current medical genetics research. This study was conducted to study the association between MTRR (A66G) polymorphism and the risk of developing acute lymphoblastic leukemia among Sudanese patients. Materials and Methods. This is a case-control study in which 150 patients with acute lymphoblastic leukemia (ALL) and 150 healthy participants as a control group were enrolled. DNA was extracted and analyzed for the MTRR (A66G) polymorphism using the real-time polymerase chain reaction. Results. Based on flow cytometry results, B-ALL was more common (79%) than T-ALL (21%). The comparison of hematological parameters in acute lymphoblastic leukemia subtypes showed a statistically significant high mean total white blood count (P=0.000) and mean blast percentage (P=0.050) in patients with T-ALL. The molecular analysis showed that the incidence of the MTRR homozygous genotypes AA and GG were higher in the patients (44% and 9.3%, respectively) compared to the control group (40% and 6.7%, respectively). In comparison, the heterozygous genotype AG was lower in the patients (46.7%) than in the control group (53.3%). However, the association between the polymorphism and acute lymphoblastic leukemia risk was not statistically significant (OR: 1.179, 95% CI 0.7459-1.865, P=0.445). Conclusions. This study concluded that MTRR A66G polymorphism was not associated with the risk of acute lymphoblastic leukemia among the Sudanese population.

Association analysis of MTHFR (rs1801133 and rs1801131) and MTRR (rs1801394) gene polymorphisms towards the development of hypertension in the Bai population from Yunnan, China

ABSTRACT Objective Hypertension is one of the leading causes of human death and disability. MTHFR and MTRR regulate folate metabolism and are closely linked to hypertension, although the relationship is inconsistent among different ethnic groups. The present study aims to investigate the effects of MTHFR C677T (rs1801133), MTHFR A1298C (rs1801131), and MTRR A66G (rs1801394) polymorphisms on hypertension susceptibility in the Bai nationality of the Yunnan Province, China. Methods This case–control study included 373 hypertensive patients and 240 healthy controls from the Chinese Bai population. The genotyping of MTHFR and MTRR gene polymorphisms was carried out by using the KASP method. The effects of genetic variations of MTHFR and MTRR genes on hypertension risk were evaluated with odds ratios (OR) and 95% confidence intervals (95% CI). Results The present study revealed that the CT and TT genotypes and T allele of MTHFR C677T locus were considerably associated with an increased risk of hypertension. In addition, MTHFR A1298C locus CC genotype could significantly increase the hypertension risk. The T-A and C–C haplotypes of MTHFR C677T and MTHFR A1298C could increase the risk of hypertension. Further stratified analysis by risk rank of folate metabolism indicated that people with poor utilization of folic acid were more prone to develop hypertension. In the hypertension group, the MTHFR C677T polymorphism was significantly associated with fasting blood glucose, fructosamine, apolipoprotein A1, homocysteine, superoxide dismutase, and malondialdehyde levels. Conclusion Our study suggested that genetic variations of MTHFR C677T and MTHFR A1298C were significantly associated with susceptibility to hypertension in the Bai population from Yunnan, China.

Association of MTR A2756G and MTRR A66G Polymorphisms With Male Infertility: An Updated Meta-Analysis.

The objective of the present study was to find out the association of folate genes MTR A2756G and MTRR A66G polymorphisms with the risk of male infertility. The databases of Google Scholar, PubMed, and Science Direct were searched to find relevant studies. Data were extracted from the eligible studies and were analyzed for pooled up odds ratio (OR) with 95% confidence interval (CI). Review Manager 5.4 was used for statistical analysis. Nineteen case-control studies were included in this meta-analysis which comprised 3621 cases and 3327 controls. Pooled analysis revealed that there is a significant association between MTR A2756G polymorphism with male infertility except for the dominant model. The ORs and 95% CI for each genetic model were as follows: 1.21 [1.03-1.42] for the allele model (G vs. A), 2.31 [1.38-3.96] for the additive model (GG vs. AA), 1.17 [0.98-1.38] for the dominant model (GG+AG vs. AA) and 2.10 [1.55-2.86] for the recessive model (GG vs. AG+AA). MTRR A66G has no noticeable association with male infertility. The current meta-analysis suggests that MTR A2756G polymorphism might be a potential risk factor for male infertility. In the future, the sample size should be increased to confirm the present results.

Cognitive impairment viz-a-viz genetic and biochemical variations in one carbon metabolic pathway: A population-based study from North India

Disturbances in the one‑carbon metabolic pathway (OCMP) have been reported to be associated with cognitive impairment (CI). The study aimed to examine the association of MTR A2756G, MTRR A66G, and CBS 844ins68 polymorphisms present at critical steps of OCMP with CI independently and in light of vitamin B12, folate deficiencies, and hyperhomocysteinemia. The study also aimed to understand gene-gene interactions among selected markers linked with OCMP in CI using multifactor dimensionality reduction (MDR) analysis. A total of 808 individuals, aged 30–70 years of either sex, were recruited from Haryana, North India. Participants were screened for CI using MMSE. Individuals with mild CI were considered as case-1 and moderate/severe CI as case-2. Sociodemographic data were collected using an interview schedule. Biochemical and genetic analyses were performed using standard protocols. In the present study, CI was not found to be associated with MTR A2756G or CBS 844ins68 polymorphisms. AG and AA+AG genotypes of MTRR A66G polymorphism, with GG as the reference genotype, were found to pose 1.97 to 2.59-folds significantly increased risk for case-1 and case-2 CI. These associations, however, lost statistical significance for normal levels of vitamin B12 and homocysteine. In MDR analysis, two-loci models with MTHFR+MTRR for case-1 and MTR+MTRR for case-2 were found to have the highest TA% and CVC. Overall, MTRR A66G polymorphism appears to be a risk factor for CI in the studied population. Vitamin B12 seems to modulate the association of CI with MTRR A66G. MDR analysis suggests the involvement methionine cycle of OCMP in CI.

Impact of Methionine Synthase Reductase Polymorphisms in Chronic Myeloid Leukemia Patients.

Highlights What are the main findings? Our objective was to determine the relationship between the methionine synthase reductase polymorphisms (MTRR and MTR) and the risk of developing chronic myeloid leukemia (CML) in Sudanese Patients. What is the implication of the main finding? Here, we report that the heterozygous and homozygous mutant genotypes of MTRR polymorphisms were associated with a decreased risk of developing CML in the Sudanese population asa protective factor.Our findings will help to increase the understanding of MTRR A66G polymorphism and its association with CML risk in the Sudanese population. Introduction： Metabolism methionine and of folate play a vital function in cellular methylation reactions, DNA synthesis and epigenetic process.However, polymorphisms of methionine have received much attention in recent medical genetics research. Objectives: To ascertain whether the common polymorphisms of the MTRR (Methionine Synthase Reductase) A66G gene could play a role in affecting susceptibility to Chronic Myeloid Leukemia (CML) in Sudanese individuals. Methods: In a case-controlled study, we extracted and analyzed DNA from 200 CML patients and 100 healthy control subjects by the PCR-RFLP method. Results: We found no significant difference in age orgender between the patient group and controls. The MTRR A66G genotypes were distributed based on the Hardy-Weinberg equilibrium (p > 0.05). The variation of MTRR A66G was less significantly frequent in cases with CML (68.35%) than in controls (87%) (OR = 0.146, 95% CI = 0.162–0.662, p < 0.002). Additionally, AG and GG genotypes and G allele were reducing the CML risk (Odds ratio [OR] = 0.365; 95% CI [0.179–0.746]; p = 0.006; OR = 0.292; 95% CI [0.145–0.590]; p = 0.001 and OR = 0.146; 95% CI [0.162–0.662]; p = 0.002 and OR = 2.0; 95% CI [1.3853–2.817]; respectively, (p = 0.000)). Conclusions: Our data demonstrated that heterozygous and homozygous mutant genotypes of MTRR polymorphisms were associated with decreased risk of developing CML in the Sudanese population.

Evaluating the Association Between Genetic Polymorphisms Related to Homocysteine Metabolism and Unexplained Recurrent Pregnancy Loss in Women.

ObjectiveTo investigate the relationship between unexplained recurrent pregnancy loss (URPL) and polymorphisms of homocysteine metabolism-related genes in women.Materials and MethodsA case–control study included 90 women with two or more consecutive unexplained pregnancy losses and 92 controlled women without miscarriage history; the female participants were in the age category of 18–35 years. The high-resolution melting technique was used to detect the single-nucleotide variants related to homocysteine metabolism disorder, namely MTHFR C677T, MTHFR A1298C, MTR A2756G, and MTRR A66G polymorphism.ResultsThe MTHFR C677T polymorphism had significantly correlation with URPL. Indeed, the frequency of the677T allele and genotypes (677CT, 677TT) in the URPL group was significantly higher than that in the control group (p < 0.05). However, the allele, as well as genotype distribution of MTHFR A1298C, MTR A2756G, and MTRR A66G polymorphisms showed no significant difference (p > 0.05). MTHFR 677CT-1298AC genotype combination led to a 9.0-fold increased risk of URPL (OR 9.0; 95% CI, 2.25–35.99; p = 0.001), while the risk increased 10.0-fold (OR 10.0; 95% CI, 1.8–55.53; p = 0.008) when participants had more than the 3 variant loci.ConclusionThe MTHFR C677T polymorphism was a risk factor for URPL, and determining the MTHFR C677T polymorphism had a potential prediction of URPL risk. Moreover, the MTHFR C677T and MTHFR A1298C joint mutants might have a synergistic effect on URPL. Conversely, there is a lack of evidence suggesting the URPL risk of MTHFR A1298C, MTR A2756G, and MTRR A66G polymorphisms.

Genotype characteristic of MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G polymorphisms in recurrent pregnancy loss

This research aimed to investigate the correlation between genotype of single nucleotide polymorphisms MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRRA66G and recurrent pregnancy loss (RPL). A case-control study was performed on 92 women suffering from URPL and 92 women who had a normal history of pregnancy. Regarding MTHFR C677T, the average numbers of alleles, heterozygous genotypes, and mutant homozygous genotypes were significantly higher in the group with RPL (p&lt;0.05), women with these genotypes had a greater incidence of having recurrent pregnancy losses 2.5 fold (OR 2.5, 95% CI, 1.27-4.94, p=0.0041), and 4.57 fold (OR 4.57, 95% CI, 1.05-27.41, p=0.0190), separately. Otherwise, the cases were also significantly higher in MTR A2756G mutant allele versus the controls (p&lt;0.05). However, in terms of the MTHFR A1298C, MTR A2756G, MTRRA66G polymorphisms, the obtained results were similar and they were not risks factor of recurrent pregnancy loss (p&gt;0.05). The polymorphism MTHFR C677T is a risk factor for the RPL in the participants. Regarding the MTHFR A1298C, MTR A2756G, and MTRR A66G polymorphisms, more research has to be done to further analyse their correlation.

Multiplex One-Step Blood Direct Asymmetric Pcr and Dual Labelled Probe Mediated Melting Curve for Mthfr C677t, A1298c and Mtrr A66g Polymorphisms Genotyping in One Tube

Multiplex One-Step Blood Direct Asymmetric Pcr and Dual Labelled Probe Mediated Melting Curve for Mthfr C677t, A1298c and Mtrr A66g Polymorphisms Genotyping in One Tube

Methionine synthase reductase A66G polymorphism and ischemic stroke in younger patients

In the past decade, stroke incidence in younger adults increased. Methionine synthase reductase (MTRR) A66G polymorphism is one of the risk factors for ischemic stroke (IS). However, clinical features of IS in MTRR A66G polymorphism are not yet studied.Objective: to investigate clinical features of IS in MTRR A66G polymorphism.Patients and methods. One hundred forty-one younger patients with IS, hospitalized in the neurological department of Sverdlovsk Regional Clinical Hospital №1, were included in the study. MTRR A66G polymorphism was detected by the real-time polymerase chain reaction in all participants.Results and discussion. MTRR A66G polymorphism was present in 83.7% of younger patients with IS. Participants with MTRR A66G polymorphism had a significantly higher prevalence of arterial hypertension (р=0.029). In addition, protein C level was significantly lower in patients with MTRR A66G mutation (р=0.001).Conclusion. The majority of younger patients with IS have MTRR A66G polymorphism. Therefore, the inclusion of MTRR A66G polymorphism screening in the diagnostic algorithm of stroke in young adults seems necessary.

Role of MTHFR C667T and MTRR A66G genes polymorphism with thyroid disorders

Thyroid disorders is the most common disease of the endocrine system. It is estimated that there are approximately 300,000 new cases of thyroid cancer worldwide. Overcome of these are females, the number of cases for thyroid disorders has been infix increasing. The aim of this study was to determine the correlation between MTHFR C677T and MTR A2756G polymorphisms involved in folic acid metabolism with thyroid disorders. We also wanted to investigate the relationship between these genetic variation and risk factors. The blood samples were collected from all cases in two different tubes: first for biochemical analysis, the second have EDTA used for DNA extraction. By Bio drop, DNA concentration and purity were measuring done, In this study be accomplished the correlation between the genetic variation of MTRR A66G gene and MTHRF C677T gene polymorphism with thyroid disorders by ARMS-PCR. In this study show increase the levels of T3 and T4 and decrease the level of TSH in patients with hyperthyroidism compare with control groups, also this table show decrease the levels of T3 and T4 but increase the level of TSH in patients with hypothyroidism compare with healthy peoples. As well as the result showed increase in levels of glucose, cholesterol and triglyceride in patients with hypothyroidism compare with healthy people, Concerning in hyperthyroidism we showed decrease in levels of glucose, cholesterol and triglyceride compare with healthy people. The association between MTHFR C677T and MTRR A66G polymorphisms and the risk of thyroid disorders showed. The 677TT genotype was associated with increased risk for both hypothyroidism (30 %) and hyperthyroidism (10 %) but in different ratio. The 677TC genotype be found in this study have same influence in hypothyroidism (60 %) and hyperthyroidism (60 %) and the 677CC genotype present in result but have different effect on study groups in hypothyroidism (10 %) and hyperthyroidism (30 %). The result also show the genotype ratio of MTRR A66G gene in cases. The GG genotype was associated with thyroid disorders for both hypothyroidism (60 %) and hyperthyroidism (40 %) but in different ratio. The AG genotype be found in this study have same influence in hypothyroidism (20 %) and hyperthyroidism (20 %) and the AA genotype present in result but have different effect on study groups in hypothyroidism (20 %) and hyperthyroidism (40 %). The study has found that the correlation and interaction between MTHFR and MTRR genes polymorphism with thyroid disorders. In addition, we found the genotype (TT) MTHFR C677T polymorphism and the genotype (GG) for MTRR A66G increased risk factors in thyroid disorders.

Associations of MTRR A66G polymorphism and promoter methylation with ischemic stroke in patients with hyperhomocysteinemia.

Patients with hyperhomocysteinemia (HHcy) have a higher risk of developing ischemic stroke (IS). The association between MTRR A66G polymorphism and promoter methylation with IS in patients with HHcy is also uncertain. The present study aimed to investigate the association between the MTRR polymorphism and methylation with IS in HHcy patients. This case-control study included a total of 304 HHcy patients (95 with IS and 209 without IS). Multivariate logistic regression analyses were applied to explore the association between MTRR polymorphism and classical atherothrombotic risk factors with the risk of IS. The log-additive and dominant models were markedly different in participants with IS compared to the control group (p = 0.031 and 0.016, respectively). The log-additive and dominant showed a significant association with IS in the low level plasma homocysteine groups (p = 0.024 and 0.014, respectively). No significant difference of methylation between IS and without IS group (p > 0.05). Patients with high plasma homocysteine had a 4.041-4.941 fold higher risk of IS (p = 0.01, 0.016 and 0.041, respectively) compared to the low plasma homocysteine group. Age, diabetes, hypertension and plasma homocysteine were the risk factors for IS in patients with HHcy (p = 0.033, 0.000, 0.001 and 0.038, respectively). MTRR A66G polymorphism and an elevated plasma plasma homocysteine level were significantly associated with an increased risk of IS in patients with HHcy. Age, diabetes, hypertension and Hcy were all found to be associated with IS.

Contribution of MTR A2756G polymorphism and MTRR A66G polymorphism to the risk of idiopathic male infertility.

Background:Methionine synthase reductase gene (MTRR A66G) polymorphism and methionine synthase gene (MTR A2756G) polymorphism have shown an association with idiopathic male infertility risk in several ethnic populations. However, their small sample sizes and inconsistent outcomes have prevented strong conclusions. We performed a meta-analysis with published studies to evaluate the associations of the 2 single nucleotide polymorphisms (SNPs) and idiopathic male infertility risk.Methods:A thorough literature search was performed up to Jun 21, 2019 with Medline, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), China Biology Medical literature (CBM), China Science and Technology Journal Database (VIP), and Chinese literature (Wan Fang) databases. Odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the strength of associations.Results:Seventeen studies including 3269 cases and 3192 controls met the inclusion criteria. Our meta-analysis showed that the MTR A2756G mutation may contribute to genetic susceptibility to the risk of idiopathic male infertility in Non-Asians, but not to Asian population, whereas the MTRR A66G polymorphism may be unrelated to idiopathic male infertility in both Non-Asian and Asian populations. In the stratified analysis by infertility type, the MTR A2756G polymorphism was a risk factor for both non-obstructive azoospermia (NOA) and oligoasthenoteratozoospermia (OAT) patients. However, the MTRR A66G polymorphism is associated with risk for OAT in Asian, but not in Non-Asian population.Conclusion:This meta-analysis suggested that the MTR A2756G and MTRR A66G polymorphisms were risk factors for idiopathic male infertility. Studies with larger sample sizes and representative population-based cases and well-matched controls are needed to validate our results.

Can the genetic polymorphisms of the folate metabolism have an influence in the polycystic ovary syndrome?

To investigate the association of the genetic variants of the folate metabolism genes (MTHFR C677T; MTHFR A1298C; MTR A2756G; MTRR A66G and RFC-1 A80G) with the development of polycystic ovary syndrome (PCOS). This study included 203 women (99 women with PCOS and 104 controls). The genotyping was performed by PCR-RFLP. Chi-squared test and multiple logistic regression were used in the statistical analysis. Haplotype analysis was conducted using the SNPstat program. The results were presented in odds ratio (OR) and confidence interval of 95% (CI-95%), with a significance level of 5% (p ≤ 0.05). The genotypic distribution of the RFC-1 A80G polymorphism showed significant difference between the two groups, showing that the heterozygous genotype (AG genotype) was most frequent in controls. The polymorphic homozygous (GG genotype) of MTRR A66G polymorphism were most frequent in controls. The T-C haplotype MTHFR C677T and A1298C polymorphisms were more frequent in the control group (OR = 0.19; CI 95% - 0.04 to 0.93 e p = 0.042). The multivariate analysis evidenced that family history of PCOS was more frequent in the PCOS group (OR = 3.29; CI 95% - 1.48 to 7.31; p = 0.003). In our casuistry, the polymorphic homozygous of MTRR A66G polymorphism gene and heterozygous of RFC-1 A80G polymorphism gene, the haplotype T-C C677T and A1298C polymorphisms of MTHFR gene, can be associated with protective factors for the disease.

Association of MTHFR C677T, MTHFR A1298C, and MTRR A66G Polymorphisms with Neural Tube Defects in Tunisian Parents

Objective: This study aims to investigate the association of 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and methionine synthase reductase (MTRR A66G) gene polymorphisms with neural tube defects (NTDs) in a Tunisian population. Methods: Genotyping was performed by polymerase chain reaction with restriction fragment length polymorphisms (PCR-RFLPs) using the restriction enzymes. Allele and genotype frequencies were compared between mothers and fathers of fetuses with NTDs with matched controls based on an association analysis using SPSS software. Results: MTHFR (C677T, A1298C) and MTRR A66G polymorphisms were found to be protector factors for NTD fetuses in the mother group. In addition, a combination of the three wild-type alleles C677/A1298/A66 has increased four-fold the incidence of NTDs (p = 0.004, OR = 3.96, 95% CI: 1.53–10.23). In the father group, MTHFR C677T was a risk factor for NTDs. However, no association was found between MTHFR A1298C, MTRR A66G, and the occurrence of this anomaly. The analysis of MTHFR C677T and MTRR A66G polymorphisms has demonstrated a significant difference in vitamin B₁₂ levels between recessive and dominant genotypes in case mothers (p < 0.05). Conclusion: Additional studies are required to better understand the roles of parental gene polymorphisms related to folate-homocysteine metabolism in the pathogenesis of NTD.

Methionine Synthase Reductase-A66G and -C524T Single Nucleotide Polymorphisms and Prostate Cancer: A Case-Control Trial

Purpose:Some variations in the sequence of methionine synthase reductase (MTRR) gene can increase the risk of various cancers such as prostate cancer. The aim of this study was to investigate the association between prostate cancer and the MTRR A66G and C524T gene single nucleotide polymorphisms (SNPs) using an in silico analysis.Methods:In this case-control study, 218 Iranian men, including 108 men with prostate cancer and 110 prostate cancer-free men, were enrolled. The MTRR A66G and C524T genotyping was performed by PCR-RFLP. Some of the bioinformatics tools were employed for the evaluation of polymorphism on the molecular aspects of the MTRR.Results:With regard to the MTRR A66G polymorphism, the genotype AG (OR: 0.85, 95% CI: 0.47-1.54, p= 0.6014), genotype GG (OR: 0.89, 95% CI: 0.42-1.87, p= 0.7512), and allele G (OR: 0.92, 95% CI: 0.63-1.35, p= 0.6686) were not associated with prostate cancer risk. However, the data for C524T SNP showed that the genotype CT was associated with prostate cancer risk (OR: 1.92, 95% CI: 1.06-3.47, p= 0.0308). Further, carriers of the allele T (OR: 1.80, 95% CI: 1.04-3.13, p= 0.0358) were associated with high risk of prostate cancer. In addition, bioinformatics analysis revealed that C524T SNP could affect some molecular aspects of the protein structure, while having no effect on the mRNA structure.Conclusion:The MTRR C524T is a genetic risk factor for prostate cancer; however, the MTRR A66G is not suggested as a suitable biomarker for prostate cancer. To obtain more reliable results, further studies are recommended to use larger sample sizes and investigate the effects of environmental factors.