A1298C Polymorphisms Research Articles

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms 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. Reviewing 14 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 MTHFR C677T and A1298C and 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 MTHFR C677T polymorphism was significantly associated with GC risk, especially in Asians, while MTHFR A1298C polymorphism was not associated with GC risk. However, in subgroup analysis by hospital-based controls, we found that MTHFR A1298C might be a protective factor for GC. After credibility assessment, the statistical association between MTHFR C677T and GC susceptibility study was classified as 'less credible positive result', while the result of MTHFR A1298C was considered unreliable. In summary, the present study strongly suggests that MTHFR C677T and A1298C polymorphisms are not significantly associated with the GC risk.

Predictive Effect of Methylene Tetrahydrofolate Reductase Variants on Vascular Related Crisis

BACKGROUND: Homocysteinemia is regarded as potential predictor for vaso-occlusive phenomenon often observed in sickle cell hemoglobinopathy. The objective was to determine the relationship of these genotypes with homocysteinemia and the predictive coefficient of these polymorphisms on the vascular-related crisis in the presence of sickle cell gene. MATERIALS AND METHODS: The case-control study comprised 89 children diagnosed with sickle disease with features of vascular crisis, 160 children without crisis and 252 apparently healthy children as the control group. The genotypes were assayed for C677T and A1298C variants and their association and predictor effect for homocysteinemia of different grades were analyzed. Sequential multiple regression model was used to assess the predictive effect. RESULTS: Homocysteine levels were significantly higher in the crisis group (P < 0.001). When compared to the wild genotype the variants depicted significantly raised homocysteine levels (P < 0.001). The prevalence of C677T was 29.9% and that for A1298 was 66.3% in the study population. The odds for crisis was 2.3 times for crisis in TT677 and 1.34 times in CC1298 variants. The genotypes revealed a significant association with different grades of homocysteinemia (P < 0.001). Plasma homocysteine depicted significant negative correlation with weight, height, body mass index and hemoglobin levels. None of the TT variants reported normal homocysteine values. Shift toward the variant form showed an increase of homocysteine levels by 7.3 units and 6.9 units for C677T and A1298C single-nucleotide polymorphisms respectively. CONCLUSION: Co-presence of methylenetetrahydrofolate reductase C677T and A1298C polymorphisms could be important predictor for homocysteinemia and thus contribute toward vascular crisis in sickle cell patients.

Türk çiftlerde infertilite ve metilentetrahidrofolat redüktaz genotipleri arasındaki ilişki

Purpose: Infertility is described as unexplained when all of the tests of a basic infertility evaluation return within normal limits and present in 15% of infertile couples. Some studies indicate that there is an association between methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) mutations and unexplained infertility in male or female grown adults. The objective of this study was to analyze the distributions of MTHFR’s C677T and A1298C genotypes in couples with unexplained fertility problems (UFP) and healthy controls.
 Materials and Methods: Two common variants C677T and A1298C of the MTHFR gene were screened in infertile couples (n =60 for C677T polymorphism; n=62 for A1298C polymorphism) and controls from the Cukurova region of Turkey. C677T and A1298C mutations in the MTHFR gene were detected by the SNP analysis (Fragment analysis) kit of the multiplex PCR amplification/ligation products. Homocysteine levels (in serum) were determined by the human hcy ELISA kit and folate values were determined by the Beckman coulter Unicel DxI 800 chemiluminescence test kit at the Central Laboratory of Balcali Hospital in Cukurova University.
 Results: In this study, an association between unexplained infertility and MTHFR C677T polymorphism was not found. However, we found an association between MTHFR A1298C polymorphism and males with UFP (%7) and controls (%19). A statistically significant difference was observed between the infertile and control groups regarding i) the folate and homocysteine values of MTHFR C677T heterozygous individuals; ii) the homocysteine values of the MTHFR C677T normal individuals; iii) the homocysteine values of MTHFR A1298C heterozygous, normal and homozygous individuals; iv) the MTHFR C677T heterozygous and normal individuals; v) the homocysteine values of MTHFR C677T normal individuals; vi) the folate values of the MTHFR A1298C heterozygous and normal individuals.
 Conclusion: The etiopathogenesis of unexplained infertility remains largely unexplored. However, the relationship of the folate/homocysteine findings with the MTHFR polymorphisms under study is not clear. The results of our study support a relationship between the MTHFR A1298C polymorphism and male fertility problems.

MTHFR A1298C polymorphism: a predictor of reduced risk of preeclampsia in Punjab, Pakistan

ABSTRACT Objectives This study aimed to investigate the genetic association between MTHFR (A1298C) SNP and preeclampsia (PE) in Punjab, Pakistan. Methods A sample of 80 pregnant women (40 healthy pregnant women and 40 with PE) was pooled for genotyping MTHFR A1298C polymorphism by using the tetra-primer amplification refractory mutation system (ARMS) PCR. The Genotypic and allelic assessments were performed using various statistical techniques. Results The AC genotype and C allele of MTHFR A1298C were found to be associated with decreased risk of PE (odds ratio [OR]: 0.31, risk ratio [RR]: 0.58, p = 0.01), and (odds ratio [OR]: 0.49, risk ratio [RR]: 0.61, p = 0.04), respectively. Conclusion In conclusion, genetic polymorphism A1298C in MTHFR may pose a protective effect in the studied population.

Impact of methylene-tetrahydrofolate reductase gene C677T and A1298C polymorphisms as a risk factor for hepatitis B virus infection

Chronic hepatitis B infection caused by Hepatitis B virus (HBV), influences over two billion people worldwide despite having an effective vaccine. With a total prevalence of 4.57%, there are 3.3 million estimated HBV carriers in Türkiye. Methylene-tetrahydrofolate reductase (MTHFR) arrange folate metabolism through nucleic acid synthesis and DNA methylation. C677T (rs1801133, p.Ala222Val) and A1298C (rs1801131, p.Glu429Ala) polymorphisms of MTHFR gene have effect of reducing the activity of enzyme. We purposed to investigate the correlation between C677T and A1298C polymorphisms of MTHFR gene with HBV infection in a Turkish population. One hundred eighteen HBV-infected participants and ninety healthy controls were incorporated in this research. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was applied to discover the genotypes of MTHFR polymorphisms. We demonstrated that T allele and CT + TT genotype frequencies of C677T polymorphism were significantly increased in HBV-infected participants than healthy controls [p = 0.015, OR (95% Cl) = 1.7 (1.11–2.79) and p = 0.020, OR (95% Cl) = 1.9 (1.10–3.42), respectively). No significant associations were noted concerning the A1298C polymorphism (p > 0.05). CC-AA composite genotype was observed to be significantly elevated in healthy controls than HBV-infected participants (32.2% vs. 13.6%, p = 0.001). In addition, the frequency of T-C haplotype was found to be considerably higher in the patient group than control group (15.8% vs 11.8%, p = 0.018). In conclusion, we found that T allele of C677T polymorphism poses a risk factor for HBV infection. We also discovered a protective impact of the CC-AA composite genotype against HBV infection and a risk effect of the T-A haplotype for HBV-infection.

MTHFR Polymorphisms and Cardiac Parameters in Patients with Diabetic Retinopathy.

Diabetes Mellitus (DM) is directly associated with cardiovascular dysfunctions and microvascular complications, such as diabetic retinopathy (DR). The association between DR and increased risks of developing cardiovascular diseases has been described. The low activity of the Methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in the metabolism of homocysteine, can lead to hyperhomocysteinemia that has already been related to cardiac outcomes and resistance to insulin. The A1298C and C677T polymorphisms in the MTHFR can reduce enzyme activity. The study aims to analyze the association between MTHFR genotypes and cardiac parameters in patients with DR. DM patients diagnosed with DR (n=65) were categorized and compared according to MTHFR genotypes A1298C (AA and AC+CC groups) and C677T (CC and CT+TT) groups; biochemical, cardiological, anthropometric, genetic, lifestyle and vitamin B9 and B12 consumption variables. Fischer's exact test and Poisson regression were performed to assess the relationship between variables. Comparing echocardiographic and electrocardiogram parameters within genotypic groups, we found a significant association between left atrial dilation and C677T polymorphism. Left atrium diameter was higher in the T allele carriers (CT+TT group), with a prevalence ratio of 0.912. This association was confirmed in the regression model, including confounding variables. The other cardiac structural and functional parameters studied were not significantly associated with the A1298C or C677T genotypes. The MTHFR C677T genotype may contribute to atrial remodeling in RD patients. We found an association between the diameter of the left atrium and the T allele of the MTHFR C677T polymorphism in patients with DR.

Вплив поліморфізма гена рецепторів ангіотензина ii типу 1 на ефективність антигіпертензивної терапії у хворих із гіпертонічною хворобою, які перенесли інфаркт міокарда за результатами довготривалого спостереження

The purpose of the study was to evaluate the effectiveness of antihypertensive therapy based on the data of daily blood pressure monitoring in patients with hypertension and a history of myocardial infarction, taking into account the A1166C polymorphism of the angiotensin II type 1 receptor gene, based on the results of long-term follow-up. Materials and methods. The study included 36 men with arterial hypertension of the 1st to 3rd degree who had suffered a myocardial infarction. The average age was 57.0 (52.0; 64.0) years, the experience of arterial hypertension – 6.3 (4.0; 15.0) years, the period after a myocardial infarction – 48.0 (12.0; 144.0) months. When determining the A1166C polymorphism of the angiotensin II type 1 receptor gene, patients were divided into 3 groups: group 1 consisted of 18 (50%) patients with the AA genotype, group 2 included 12 (33.3%) patients with the AС genotype, and group 3 – 6 (16.7%) patients with СС genotype of angiotensin II type 1 receptor gene. Daily blood pressure monitoring was carried out at the beginning of the study and after 38 months. Results and discussion. At the beginning of the study, based on the results of daily blood pressure monitoring, it was found that in the group as a whole, the levels of systolic blood pressure and diastolic blood pressure, the pressure load index – the diastolic blood pressure time index corresponded to the target values according to the median, but the pressure load indices for systolic blood pressure exceeded the normal range. Against the background of long-term antihypertensive therapy, a reliable decrease in systolic blood pressure levels was established for all time periods of the day, especially during the daytime. A significant decrease in the values of the pressure load indices was established – the time index of systolic blood pressure at daytime (delta -10.49%, which was -27.9%) and the area index of systolic blood pressure at daytime (delta -34.89 mm Hg x h, which was -32.0%) (p <0.05). When analyzing the effectiveness of long-term antihypertensive therapy depending on the A1166C polymorphism of the angiotensin II type 1 receptor gene, it was established that the highest percentage of achieving the target blood pressure level (66.7%) in combination with the normalization of the circadian blood pressure rhythm was determined in patients with the AA genotype of the AGTR1 gene. Among patients with AC genotype, 33.3% reached the target blood pressure levels, but it was not possible to achieve normalization of blood pressure variability and pathological patterns of the circadian rhythm of blood pressure persisted, which are signs of a prognostically unfavorable course of the disease. Among patients with CC genotype of the AGTR1 gene, against the background of long-term treatment, 33.3% achieved the target level of blood pressure, in general, the group normalized the degree of nocturnal decrease in blood pressure, but only a decrease in the levels of systolic blood pressure and diastolic blood pressure during the day in combination with increased values of pressure load indices was observed, which indicates insufficiently effective control of arterial hypertension. Conclusion. During the long-term observation of patients with hypertension and a history of myocardial infarction, an assessment of the effectiveness of antihypertensive therapy was carried out taking into account the A1166C polymorphism of the AGTR1 gene based on the results of daily blood pressure monitoring

Clinical Pharmacogenetics of Angiotensin II Receptor Blockers in Iraq.

Clinical pharmacogenetics is a rapidly growing field that focuses on the study of genetic variations and their impact on drug metabolism, efficacy, and safety. Angiotensin II receptor blockers (ARBs) are commonly used to treat hypertension in Iraq but not all patients respond equally to these drugs. This article aims to review the current evidence on the clinical pharmacogenetics of ARBs in Iraq and its implications for personalized medicine. We conducted a literature review of studies on the genetic variations that affect the response to ARBs in Iraq. We also reviewed the prevalence of these genetic variants in the Iraqi population and discussed the potential clinical implications for personalized medicine. The most studied genetic variations associated with ARB response in Iraq are the angiotensin-converting enzyme gene insertion/deletion polymorphism and the angiotensin II type 1 receptor gene A1166C polymorphism. The angiotensin-converting enzyme gene insertion/deletion polymorphism is associated with variability in response to ARBs, while the angiotensin II type 1 receptor A1166C polymorphism is associated with an increased risk of cardiovascular events in patients treated with ARBs. The prevalence of these genetic variants in the Iraqi population varies widely depending on the region and ethnic group. The clinical pharmacogenetics of ARBs in Iraq suggests that pharmacogenetic testing could improve the selection and dosing of ARBs in Iraqi patients, leading to better patient outcomes and cost-effective healthcare.

Polymorphisms in the Renin-Angiotensin System and eNOS Glu298Asp Genes Are Associated with Increased Risk for Essential Hypertension in a Mexican Population.

Essential hypertension is the result of modifiable and genetic factors, and it is associated with increased risk for atherothrombosis. Some polymorphisms are associated with hypertensive disease. The objective was to analyze the association between eNOS Glu298Asp, MTHR C677T, AGT M235T, AGT T174M, and A1166C and ACE I/D polymorphisms with essential hypertension in the Mexican population. In the present study, 224 patients with essential hypertension and 208 subjects without hypertension were included. The Glu298Asp, C677T, M235T, T174M, A1166C, and I/D polymorphisms were determined by the PCR-RFLP technique. We found statistical differences in age, gender, BMI, systolic and diastolic blood pressure, and total cholesterol between control and cases. However, we found no significant differences in HbA1c and triglycerides between both groups. We observed statistical significant differences in the genotype distribution of Glu298Asp (P = 0.001), I/D (P = 0.02), and M235T (P = 0.004) polymorphisms between both groups. In contrast, there were no differences related to distribution of genotypes of MTHFR C677T (P = 0.12), M174T (P = 0.46), and A1166C (P = 0.85) between cases and control groups. We identified that Glu298Asp, I/D, and M234T polymorphisms represented an increased risk for essential hypertension and those genetic variants could contribute to the presence of endothelial dysfunction and vasopressor effect, hyperplasia, and hypertrophy of smooth muscle cells, which had an impact for hypertension. In contrast, we found no association between C677C, M174T, and A1166C polymorphisms and hypertensive disease. We suggested that those genetic variants could be identified in individuals with high risk to avoid hypertension and thrombotic disease.

Genetic Variants Associated with High Susceptibility of Premature Ischemic Stroke.

Several polymorphisms had been associated with an increased risk of ischemic stroke, but results are inconclusive. The aim of this study was to examine the association between AGTR1 A1166C and TSP-1 N700S polymorphisms and ischemic stroke in a young Mexican population. In a case-control study, 250 patients ≤ 45 years of age with ischemic stroke and 250 controls matched by age and gender were included. The polymorphisms were determined in all participants by polymerase chain reaction. There were statistical differences in genotype distribution (p = 0.01) and allele frequency (p = 0.001) of AGTR1 A1166C polymorphism. In contrast, there was a similar genotype distribution (p = 0.96) and allele frequency (p = 0.76) of the TSP1 N700S genetic variant between groups. Hypertension (p = 0.03), smoking (p = 0.02), and family history of atherothrombotic disease (p = 0.04) were associated with stroke, but not diabetes (p = 0.30) and dyslipidemia (p = 0.08). This is the first study in Mexican population to explore several genetic variants in young patients with ischemic stroke. Our results suggest that polymorphisms in the renin-angiotensin-aldosterone system could contribute to premature hypertension, endothelial dysfunction, atherothrombosis, vasoconstriction, smooth muscle cell migration, and proliferation. In contrast, polymorphisms in the coagulation factors are not associated with ischemic stroke. Environmental factors such as diabetes and dyslipidemia could be less important in the pathogenesis of ischemic stroke at a young age. We suggest that those polymorphisms should be determined in individuals with a family history of thrombosis to avoid the stroke development. Therefore, genotype-environmental combination could determine several possible phenotypes at different moments in life.

Association between maternal MTHFR C677T/A1298C combination polymorphisms and IVF/ICSI outcomes: a retrospective cohort study.

What are the roles of maternal 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C combination polymorphisms on the embryological and clinical outcomes of IVF/ICSI? Our study reveals for the first time that the oocyte maturation potential gradually decreases with a reduction of maternal MTHFR activity determined by combined C677T/A1298C polymorphisms, while embryo quality was worse in women with intermediate MTHFR activity. Although many previous studies have explored the association between MTHFR polymorphisms and IVF/ICSI outcomes, the results remain contradictory due to inadequate samples, no adjustment for potential confounders and/or the study of C677T and A1298C separately. Few studies have systematically investigated the exact role of MTHFR activity determined by combined C677T/A1298C polymorphisms on the embryological and clinical outcomes of IVF/ICSI. This is a retrospective cohort study investigating 1160 women who were referred for MTHFR genotyping and IVF/ICSI treatment at Peking University Third Hospital from May 2017 to May 2020. Women who were referred for MTHFR genotyping and their first IVF/ICSI treatment at our hospital were included and those undergoing preimplantation genetic testing cycles were excluded. The included women were divided into different cohorts according to their C677T, A1298C and combined C677T/A1298C genotypes. The embryological outcomes, including oocytes retrieved, metaphase II oocytes, oocyte maturation rate, normal fertilization rate and transplantable embryo rate, were evaluated by generalized linear regression models. The clinical outcomes, including biochemical pregnancy rate, clinical pregnancy rate and live birth rate, were evaluated by log-binomial regression models. All outcomes were adjusted for potential confounders. Women with the combined 677TT/1298AA genotype (hereafter abbreviated as TT/AA, as with other combined genotypes), whose enzyme activity was the lowest, had a lower oocyte maturation rate compared with those with the wild-type genotype (P = 0.007). Moreover, the oocyte maturation rate decreased linearly with the decline in MTHFR enzyme activity determined by combined C677T/A1298C genotypes (P-trend = 0.001). The combined CC/AC, CC/CC&CT/AA and CT/AC genotypes with intermediate enzyme activity were associated with a lower transplantable embryo rate (P = 0.013, 0.030 and 0.039, respectively). The differences in clinical outcomes between women with wild-type genotype and combined C677T/A1298C variant genotypes were not significant. Our study population had comparable embryological outcomes but worse clinical outcomes than other women undergoing IVF/ICSI treatment at our hospital. Therefore, the results related to the clinical outcomes should be generalized with caution. In addition, we did not detect the folate concentration of each patient during pregnancy. However, this might not have much influence on our results because almost all of our study participants took sufficient folic acid around pregnancy. We provide a holistic view of the effect of MTHFR C677T and A1298C polymorphisms on the IVF/ICSI outcomes, which can contribute to providing reasonable folic acid supplementation suggestions for women with different MTHFR genotypes, especially for those with a low oocyte maturation rate and/or low embryo quality. This work was funded by the National Natural Science Foundation of China (31871447, and 82101677), the National Key Research and Development Program (2019YFA0801400) and the Natural Science Foundation of Beijing Municipality (7202226). The authors declare that they have no competing interests. N/A.

EFFECT OF POLYMORPHIC VARIANTS OF AGT2R1 GENE ON HEMODYNAMIC PARAMETERS IN PREMATURE CHILDREN

Relevance. Maintaining hemodynamic in premature infants who are being treated in intensive care units is one of the significant challenges in the practice of modern neonatologists and intensivists. The study of AGT2R1 gene polymorphism can help predict the course of organ dysfunction and prevent the development of adverse clinical consequences.
 The aim is to study the effect of AGT2R1 gene polymorphism on hemodynamic parameters in premature children with bacterial infections.
 Subjects and methods. A prospective cohort study included 143 prematurely born children with bacterial infections: main groups (n=40) had arterial hypotension, control group (n=103) had no arterial hypotension. All patients underwent a standard complex of clinical and laboratory research methods and PCR in order to investigate the A1166C polymorphism of the AGT2R1 gene.
 Results. The study has revealed that the CC genotype of AGT2R1 occur significantly more often in premature children with arterial hypotension than in the control group (OR 10.17, p=0.027). As a result of intragroup analysis among the infants with arterial hypotension, stratified according to polymorphic variants of the AGT2R1 gene, we did not find any significant differences in medico-demographic indicators, the frequency of resuscitation measures, hemodynamic indicators. However, prematurely born children with AC+CC genotype compared to carriers of the AA variant genotype had a lower cardiac index (4.5 vs. 3.5 ml/min*m2, p=0.04), which indicates the influence of myocardial dysfunction on the occurrence arterial hypotension
 Conclusion. A1168C polymorphism of the AGT2R1 gene affects the hemodynamic disorders in premature children with bacterial infections. Further multifaceted studies on a larger sample of patients are required to confirm this hypothesis.

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.

CTH G1208T and MTHFR A1298C polymorphisms are associated with a higher risk of a first myocardial infarction with fatal outcome among women.

Cystathionine-gamma-lyase (CSE) in the transsulfuration pathway generates hydrogen sulfide (H2S), suggested regulating cardiovascular function. The G1208T polymorphism in the CTH gene, rs1021737, has, in addition toMTHFR, been found to increase homocysteine, related to myocardial infarction (MI) risk. This study aimed, for the first time, to investigate the associations of the polymorphisms CTH G1208T, MTHFR C677T, and A1298C with the prospective risk of developing a fatal or non-fatal first MI. This case-referent study included 545 cases later developing a first-ever MI and 1,054 referents from the Northern Sweden Health and Disease Study. Fatal MI was defined as death within 28days after MI symptoms. Women, but not men, had a positive association between fatal MI and the CTH G1208T, odds ratio [95% confidence interval] 3.14 [1.16-8.54] for heterozygotes, and the dominant model 3.22 [1.22-8.51], and for the MTHFR A1298C heterozygotes 3.24 [1.26-8.34] and the dominant model 2.63 [1.06-6.50]. The MTHFR C677T polymorphism was not related to MI. This study indicates that the minor alleles of CTH G1208T and MTHFR A1298C polymorphisms are associated with a higher risk for a fatal MI among women but not for non-fatal MI. No association was found in men.

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.

Association between MTHFR polymorphism and seizure control in epileptic patients with hyperhomocysteinaemia

The aim of this study was to investigate possible associations between MTHFR polymorphism and seizure control of epileptic patients with hyperhomocysteinaemia. A total of 81 epileptic patients with hyperhomocysteinaemia treated with oxcarbazepine monotherapy were enrolled in this study. All patients were offered vitamin B supplementation (2.5 mg/d folate and 1.5 mg/d mecobalamine) for six months. MTHFR C677T and A1298C polymorphisms, serum homocysteine, folate and vitamin B12 levels as well as seizure frequency and score based on the Hamilton depression scale (HAMD) were evaluated at baseline and after six months of follow-up. Spearman correlation analysis showed that the extent of decline of seizure frequency positively correlated with a dynamic change in serum homocysteine concentration between baseline and after six months of follow-up (t=0.241, p=0.015 [Spearman’s coefficient]). For the MTHFR C677T polymorphism, compared to the CC genotype, the TT genotype was associated with a significant downtrend of homocysteine (19.69 vs 10.28 mmol/L, p=0.006) and uptrend of folate (6.21 vs 2.49 ng/mL; p=0.004). The decrease in homocysteine (17.94 vs 12.52 mmol/L, p=0.001) and increase of folate (5.08 vs 2.86 ng/mL; p=0.003) were significantly greater in patients with the T allele compared to those with the C allele. Also, the TT genotype (2.33 vs 1.4, p=0.056) and T allele (1.95 vs 1.38, p=0.037) were associated with a greater decrease in seizure frequency compared to the CC genotype or C allele. The A1298C polymorphism alone was not associated with elevated homocysteine or decreased folate levels at baseline, and showed little association with response to vitamin B supplementation in epileptic patients with hyperhomocysteinaemia. However, in patients with combined 677TT/1298AA or 677TT/1298AC polymorphisms, the changes in homocysteine and folate levels and seizure frequency were more obvious. MTHFR C677T polymorphism was associated with seizure control in epileptic patients with hyperhomocysteinaemia; individuals with the 677TT genotype or T allele demonstrated better seizure control.

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.

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.

Association of Angiotensin II Type 1 Receptor (AT1R) Gene Polymorphism with Angiotensin II Serum Levels in Patients with Essential Hypertension.

Essential hypertension (EH) is a multifactorial, polygenic condition, and is one of the most important comorbidities that contributes to stroke, myocardial infarction, cardiac failure, and renal failure. The continuous increasing rate of morbidity and mortality associated with EH presents an unmet need of population-based studies to explore pathophysiology as well as newer strategies for better diagnosis, prognosis and treatment. This study aimed to determine genotype and allele frequencies of A1166C polymorphism of AT1R gene in Indian patients with EH and correlated with serum levels of Angiotensin II. A total of 200 patients with EH and 200 age- and gender-matched control individuals were included in this study from the General Medicine Department Outpatient at Narayana Medical College and Hospital, Nellore, Andhra Pradesh, India. Patients with systolic blood pressure (SBP) ≥ 140mmHg and/or diastolic blood pressure (DBP) ≥ 90mmHg were considered as hypertensive. The findings of this study revealed significantly increased risk of C/A heterozygote and allele C in both men and women. Moreover, both men and women patients with EH showed higher serum levels of Angiotensin II with C/A as well as AA genotypes. These findings indicate a significant association of 1166 C/A polymorphism of the AT1R gene with increased risk of hypertensionin Indian population.