Non-syndromic Cleft Lip and Palate Patients of the North Indian Population and the Association of Methylenetetrahydrofolate Reductase Gene.

INTRODUCTION: Cleft lip and palate (CLP) is a common congenital anomaly characterized by incomplete fusion of the lip and/or palate during embryonic development. The etiology of CLP is multifactorial, involving genetics and different environmental factors. The methylenetetrahydrofolate reductase (MTHFR) gene has been proposed as a candidate gene associated with CLP due to its involvement in folate metabolism and DNA methylation processes. However, the association between MTHFR gene variants and CLP in non-syndromic patients in the North Indian population remains unclear. AIM AND OBJECTIVES: This research aimed to see the association between MTHFR gene polymorphisms in non-syndromic patients with CLP in the North Indian population. MATERIALS AND METHOD: A case-control observational design comprised 50 CLP patients (cases) and 50 healthy individuals without CLP (controls). Blood samples were collected from patients visiting two hospitals. Genomic DNA was extracted from collected peripheral blood samples, and the genotyping of MTHFR gene polymorphisms (specifically, C677T) was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The allelic and genotypic frequencies of MTHFR gene variants were compared between cases and controls using appropriate statistical tests. RESULT: This research revealed a significant association between MTHFR gene polymorphism and CLP in the North Indian population. The odds for the genotypes reach statistical significance, suggesting that the MTHFR gene variant may play a major role in this population's susceptibility to non-syndromic CLP. CONCLUSION: This study provides evidence for a linkage between the MTHFR gene C677T polymorphism and an increased risk of CLP in non-syndromic patients in the North Indian population. These findings do support the involvement of MTHFR gene variants in the etiology of CLP. In the future, more research is warranted to elucidate the underlying mechanisms linking MTHFR gene variants to CLP and to explore potential gene-environment interactions in this context.

Association between Methylenetetrahydrofolate Reductase (MTHFR) and 5-Methyltetrahydrofolate-Homocysteine Methyltransferase Reductase (MTRR) Polymorphisms in Iraqi Patients with COVID-19.

Background: The methylenetetrahydrofolate reductase (MTHFR) gene is an essential gene in the metabolism of folate-homocysteine. Recently, the level of homocysteine was found to be a significant marker in the follow-up of COVID-19 infection. Thus, this study aimed to detect the effect of genetic polymorphisms for single nucleotide polymorphisms (SNPs) (c.66A>G, c.1298A>C, and c.677CT) on COVID-19 infection. Methods: Blood samples were collected from 270 patients with COVID-19 in the medical center of Al-Shifa (Baghdad, Iraq) from November 2020 to March 2021. Tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique was used for the detection of genotypes of SNPs. The odds ratio (OR) was used to detect the relationship between SNPs and COVID-19 infections. Haplotype analysis was performed by SHEsis software. Results: There was a significant difference between mild/moderate cases and severe/critical cases for ages (35-45), (46-55), and (56-65) years (P<0.0001, P=0.01, and P=0.006, respectively). The results showed significant differences in the T allele for SNP c.677>C (P<0.0001 and OR=4.58). The C allele for SNP c.1298A>C indicated significant differences (P<0.001 and OR=3.15). Besides, the G allele for SNP c.677C>T showed significant differences (P<0.001 and OR=6.64). Consequently, these SNPs showed a predisposition to the development of COVID-19 infection. With regard to the C-A-A, T-A-A and T-C-G haplotypes indicated significant differences between the control and patient groups. The C-A-A was related to a decreased risk and indicated a protective effect against COVID-19 infection development (P<0.0001 and OR=0.218). The increased risk was associated with T-A-A and T-C-G haplotypes and indicated the risk impact on COVID-19 infection development (P<0.0001, P=0.004, and OR=15.5, OR=6.772, respectively). Furthermore, the linkage disequilibrium (LD) for SNPs was studied, and the complete D' value was 99. Conclusion: The genetic polymorphisms of SNPs (c.66A>G, c.1298A>C, and c.677C>T) in the Iraqi population were associated with COVID-19 infection.

Association of Maternal Dietary Habits and Infant MTHFR Gene Polymorphisms with Ventricular Septal Defect in Offspring: A Case-Control Study.

This study aimed to explore the association of maternal diet, infant MTHFR gene polymorphisms, and their interactions with the risk of ventricular septal defects (VSDs). This case-control study recruited 448 mothers of VSD children and 620 mothers of healthy counterparts. Multivariable-adjusted logistic regression models were constructed to examine the association between maternal dietary habits during the first trimester of gestation, MTHFR gene polymorphisms, and VSD. Gene-environment interaction effects were analyzed through logistic regression models, with false discovery rate p-value (FDR_p) < 0.05. Maternal excessive intake of fermented bean curd (OR = 2.00, 95%CI: 1.59-2.52), corned foods (OR = 2.23, 1.76-2.84), fumatory foods (OR = 1.75, 1.37-2.23), grilled foods (OR = 1.34, 1.04-1.72), and fried foods (OR = 1.80, 1.42-2.27) was associated with an increased risk of VSD. Regular intake of fish and shrimp (OR = 0.42, 0.33-0.53), fresh eggs (OR = 0.58, 0.44-0.75), soy products (OR = 0.69, 0.56-0.85), and dairy products (OR = 0.71, 0.59-0.85) was found to reduce the occurrence of VSD. Moreover, MTHFR gene polymorphisms at rs2066470 (homozygous: OR = 4.28, 1.68-10.90), rs1801133 (homozygous: OR = 2.28, 1.39-3.74), and rs1801131 (heterozygous: OR = 1.75, 1.24-2.47; homozygous: OR = 3.45, 1.50-7.95) elevated offspring susceptibility to VSDs. Furthermore, significant interactions of MTHFR polymorphisms with maternal dietary habits were observed, encompassing corned foods, fermented bean curd, fried foods, and grilled foods. Maternal dietary habits; MTHFR polymorphisms at rs2066470, rs1801131, and rs1801133; and their interactions were significantly associated with the occurrence of VSDs in offspring.

Discovery of Methylenetetrahydrofolate Reductase (MTHFR) Deficiency in Individuals With Common Psychiatric Comorbidities: A Retrospective Case Review.

INTRODUCTION: A retrospective analysis was conducted of a data set collected in an outpatient behavioral health clinic to assess medication metabolism and methylenetetrahydrofolate reductase (MTHFR) and to see if there was a correlation with certain diagnoses and/or gender. METHOD: The outpatient routine completed genetic testing on their patients and the test results were later collected through a third-party company, which completed the pharmacogenomic test analyzing genetic variations in DNA, medication metabolism, and an MTHFR deficiency. RESULTS: This study reviewed 186 patients seen in an outpatient setting who were tested for an MTHFR deficiency and compared their psychiatric diagnoses and the number of failed medication attempts. Of those 186 patients, 77 had normal MTHFR enzyme function, 85 were found to have a moderate MTHFR deficiency, and 24 had a severe MTHFR deficiency. Those with a severe MTHFR deficiency had a higher number of medication trials as compared to those without the deficiency and there were overall more patients with a moderate MTHFR deficiency in this data set. CONCLUSION: Currently, MTHFR deficiency is not commonly tested due to lack of insurance coverage and provider knowledge, and due to the cost of the test itself. Thus, the diagnosis can often be missed.

Meta-analysis of MTHFR C677T polymorphism and type 2 diabetes mellitus in MENA region.

BACKGROUND AND AIMS: The association of the C677T polymorphism of the Methylenetetrahydrofolate Reductase (MTHFR) gene with susceptibility to type 2 diabetes mellitus (T2DM) has been widely debated. Therefore, our aim is to conclusively resolve this controversy in the Middle East and North Africa region population through a meta-analysis. MATERIEL AND METHODS: We identified relevant articles by searching literature databases, such as PubMed, Web of Science, and Science Direct, to retrieve studies that examined the association between the MTHFR C677T polymorphism and the risk of developing T2DM. Using meta-analysis, we calculated the odds ratio (OR) and confidence interval (CI) values of these studies to assess the susceptibility to T2DM related to the C677T polymorphism of MTHFR gene. RESULTS: In this meta-analysis, we included a total of 13 publications comprising 2072 T2DM patients and 2164 control subjects. The results of the meta-analysis suggested that there is a significant association between the C677T polymorphism and T2DM risk in overall comparisons for allele contrasts (T vs C): OR = 1.25, 95% CI = 1.04-1.50, p = 0.015 and homozygous (TT vs CC): OR = 1.44, 95% CI = 1.01-2.05, p = 0.038). Subgroup analysis revealed that the C677T polymorphism is associated with a risk of T2DM in Asian populations, while there is no significant association between this polymorphism and T2DM in Caucasian and African populations. Furthermore, there was no evidence of publication bias. CONCLUSION: Our study's results suggest that the allele contrast of the C677T polymorphism of the MTHFR gene is associated with an increased risk of T2DM in the overall population, particularly among Asians.

Congenital septal defects in Karachi, Pakistan: an update of mutational screening by high-resolution melting (HRM) analysis of MTHFR C677T.

BACKGROUND: Congenital heart defects (CHDs) are the heart structural malformations present at birth. Septal defects account for 40% of CHD, including atrial, ventricular and atrioventricular septal defects. In Pakistan, the prevalence of CHD is 3.4 in 1000, and a study estimated that 60,000 babies are born with CHD annually. Methylenetetrahydrofolate reductase (MTHFR), a chief enzyme, involved in the folate metabolism. The missense mutation, C677T (rs1801133), exists in MTHFR gene, results in a MTHFR thermolabile variant having low enzymatic activity. The study is aim to identify the MTHFR C677T variant association with septal defects. METHODS: Samples of 194 CHD patients (age [Formula: see text]= 5.8 ± 5.1) and 50 normal echo controls (age [Formula: see text]= 6.0 ± 4.9), confirmed by pediatric consultant, were collected. Extracted DNA, quantified by agarose gel electrophoresis and nanodrop, was screened for SNP by high-resolution melting (HRM). Further, HRM results were confirmed using restriction analysis and sequencing. HRM was simply and precisely genotyped the samples within 3 h at low cost. RESULTS: Genotypic data suggested that heterozygous mutant (CT) was frequent in congenital septal defect patients (0.26) which was higher than controls (0.143), p > 0.05. Mutant (TT) genotype was not found in this study. CONCLUSIONS: rs1801133 has lack of significant association with congenital septal defects. The absence of TT genotype in this study suggesting the role of natural selection in targeted population. HRM is an easy, fast and next generation of PCR, which may be used for applied genomics.

Enhanced recovery in patients with gestational diabetes mellitus and MTHFR 677 TT genotype after taking high-dose folic acid supplements during mid-late pregnancy: an open-label interventional study.

Objective: To explore the relationship between folic acid supplementation and the recovery rate of gestational diabetes mellitus (GDM) in women with methylenetetrahydrofolate (MTHFR) 677 TT genotypes in mid-late pregnancy. Methods: 9, 096 pregnant women were recruited with their MTHFR gene genotyped. 5,111 women underwent a 75-g oral glucose tolerance test (OGTT) and 2,097 were confirmed with GDM. The association between MTHFR genotypes and GDM risk was estimated using logistic and log-binomial regression, with age and parity set as the covariates to control their confounding effects. Further assessment of GDM risk on glucose levels was done using the ANCOVA model. As an open-label intervention study, 53 GDM patients with TT genotype were prescribed 800µg/day of folic acid as the high-dose group, while 201 GDM patients were given 400µg/day as the standard-dose group at their 24-28 weeks of pregnancy. A rate ratio (RR) of GDM recovery was estimated at each available time point for both groups. The time-to-GDM persistence events were analyzed with the Kaplan-Meier method and Cox-regression model. The trend of glucose levels over time was estimated using the linear model. Results: MTHFR 677 TT genotype has no significant association with the glucose levels and GDM risk, with an adjusted OR of 1.105 (95% CI 0.853, 1.431; p=0.452) and an adjusted PR of 1.050 (95% CI 0.906, 1.216; p=0.518) compared to the wildtype CC group. Patients in the high-dose group (n=38; 15 drop-outs; 40.69 days (95% CI 33.22, 48.15)) recovered from GDM approximately 27 days faster than those in the standard-dose group (n=133; 68 drop-outs; 68.09 days (95% CI 63.08, 73.11)). Concomitantly, the RR of GDM recovery rose and reached 1.247 (95% CI 1.026, 1.515) at 100 days of treatment with the standard-dose group as reference. Conclusion: High-dose folic acid supplement intake in mid-late pregnancy is associated with faster GDM relief in patients with MTHFR 677 TT genotype compared to the standard dose, which would be served as a novel and low-cost alternative therapy for the treatment of GDM.

Role of MTHFR 677C>T and 1298A>C gene polymorphisms on renal toxicity caused by lead exposure in wastewater treatment plant workers.

Environmental and occupational lead (Pb) exposures continue to pose major public health problems. Wastewater treatment plant (WWTP) workers proved are exposing to high Pb concentrations in sludge departments. The aim of the work was to investigate the role of MTHFR C677T and MTHFR A1298C gene polymorphisms on alteration of oxidative stress and homocysteine levels in WWTP workers exposed to high Pb concentrations, and study its relations with renal functions. The study included 90 WWTP workers from Abu-Rawash WWTP. Homocysteine, creatinine, urea, malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured. Polymorphisms of MTHFR C677CT and MTHFR A1298C genes were studied using PCR/RFLP. Urine Pb concentrations were also measured. About 32.2% of the workers were with detectable Pb levels. Pb, homocysteine, and MDA levels were significantly higher among workers carrying TT polymorphism compared to other MTHFR C677T gene polymorphisms, while TAC was significantly lower among them compared to other polymorphisms. The same results were found among workers carrying CC compared to other MTHFR A1298C gene polymorphisms. WWTP workers carrying MTHFR 677TT and MTHFR 1298CC are more susceptible to elevation of homocysteine and the urinary Pb compared to the workers with the other polymorphisms. Furthermore, those workers were found to have increase in urea and creatinine. Therefore, MTHFR C677T and MTHFR A1298C gene polymorphisms could be used for prediction of the susceptibility to the risk of kidney impairments among WWTP workers in the sludge departments caused by their exposure to high Pb in their workplace.

Association of MTHFR C667T Polymorphism, Homocysteine, and B Vitamins with Senile Cataract.

Senile cataract has become the leading cause of visual impairment and even blindness in the world, but there are few reports on its relationship with methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms. This study is aimed to investigate the correlation between MTHFR gene polymorphisms or its enzyme metabolites and senile cataract. From January 2019 to June 2020, 663 patients with senile cataract at the Mianyang Central Hospital were enrolled as the observation group, and 646 healthy subjects were randomly selected as the control group. MTHFR gene polymorphisms (i.e., CC, CT, or TT genotypes) and serum homocysteine (HCY), folic acid (FOL), vitamin B12 (VitB12), and vitamin B6 (VitB6) levels were detected. The mutation rate of MTHFR C677T and HCY levels in the observation group were significantly higher than those in the control group, whereas FOL, VitB12, and VitB6 were significantly lower. With an increase in the MTHFR C677T mutation, HCY showed an upward trend, whereas FOL and VitB12 showed a decreasing trend in both the observation and control groups. Multiple logistic regression analysis showed that HCY and FOL were associated with senile cataract and MTHFR mutations; VitB12 was only associated with senile cataract. Compared to that with the CC genotype, CT and TT genotypes were associated with an increased senile cataract risk. Monitoring MTHFR gene polymorphisms and changes in serum HCY, FOL, and VitB12 levels could provide references in predicting senile cataract.

Folate-dependent hypermobility syndrome: A proposed mechanism and diagnosis.

Hypermobility involves excessive flexibility and systemic manifestations of connective tissue fragility. We propose a folate-dependent hypermobility syndrome model based on clinical observations, and through a review of existing literature, we raise the possibility that hypermobility presentation may be dependent on folate status. In our model, decreased methylenetetrahydrofolate reductase (MTHFR) activity disrupts the regulation of the ECM-specific proteinase matrix metalloproteinase 2 (MMP-2), leading to high levels of MMP-2 and elevated MMP-2-mediated cleavage of the proteoglycan decorin. Cleavage of decorin leads ultimately to extracellular matrix (ECM) disorganization and increased fibrosis. This review aims to describe relationships between folate metabolism and key proteins in the ECM that can further explain the signs and symptoms associated with hypermobility, along with possible treatment with 5-methyltetrahydrofolate supplementation.

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.

Biochemical Association of MTHFR C677T Polymorphism with Myocardial Infarction in the Presence of Diabetes Mellitus as a Risk Factor.

Myocardial infarction (MI) is a cardiovascular disease that occurs due to the blockage of the coronary artery. Subsequently, cardiac muscles receive a lower oxygen supply, which leads to the death of cardiac muscles. The etiology of MI is linked to various environmental, occupational, and genetic factors. Various studies have been conducted on the polymorphism of genes involved in MI. Previous studies have shown that different variants of the methylene tetrahydrofolate reductase (MTHFR) gene are involved in causing MI by altering the metabolism of folate and homocysteine. However, the genetic polymorphism of MTHFR C677T (rs1801133) and its association with MI in the presence of diabetes mellitus (DM) as a risk factor still needs to be investigated. This study recruited 300 participants who were divided into three groups, i.e., the control, MI, and MI-DM. The blood samples collected from the study participants were subjected to various biochemical tests and their clinical parameters were monitored. MTHFR C677T (rs1801133) genotyping was performed by Tetra ARMS PCR using predetermined primers. The MTHFR C677T (rs1801133) polymorphism was associated with MI in the presence of DM as a risk factor among the participants. The MTHFR C677T (rs1801133) T/T homozygous genotype was found to be significant among MI patients in the presence of DM as a risk factor.

The methylenetetrahydrofolate reductase C677T and A1298C genetic polymorphisms and plasma homocysteine in Alzheimer's disease in an Algerian population.

BACKGROUND: The etiology of Alzheimer's disease (AD) is multifactorial. The most important challenge of research is the identification of potential biomarkers associated with AD pathogenesis that may significantly contribute to early diagnosis of the disease. We aim to explore an eventual association of the C677T and A1298C genetic polymorphisms in the MTHFR gene with AD risk in an Algerian population. METHODS: This case-control study involved comparing a group of 106 patients that had developed AD to another group of 104 non-demented individuals. The MTHFR genotypes were determined using PCR-RFLP method. Additionally, the homocysteine level was evaluated. RESULTS: Genotypes analysis did not show an association for both MTHFR677CT and 677TT variants with AD risk (OR = 1.12; p = 0.66; OR = 1.76; p = 0.09) respectively. As expected, the 677CC wild type genotype showed a protective role against AD (OR = 0.52; p = 0.03). For 1298AC MTHFR variant, the distribution of different genotypes did not show a statistical significant difference between the two cohorts. However the silmutaneous carrier, CT/AC presented association with AD (OR = 5.96; p = 0.05). On the other hand, carrier-state of MTHFR T allele showed a relationship with AD (OR = 1.98; p = 0.02). Additionally, hyperhomocysteinemia seems to be a risk factor for AD (OR = 1.08; p = 0.02). CONCLUSION: Our exploration reveals that the silmutaneous carrier, CT/AC, carrier-state of MTHFR T allele, and hyperhomocysteinemia seem to be risk factors for AD.

MTHFR C677T polymorphism and cerebrovascular lesions in elderly patients with CSVD: A correlation analysis.

Plasma homocysteine (Hcy) has been identified as a potential risk factor for cerebral small vessel disease. Cerebral small vessel disease (CSVD) leads to cognitive impairment, depression, and other symptoms and is a common disease in middle-aged and elderly people. To investigate the relationship between 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and CSVD in elderly patients, plasma levels of homocysteine (Hcy) and MTHFR genotyping were assessed. MRI and MRA were performed at the same time to analyze the relationship between different genotypes and cerebrovascular lesions. We showed that Hcy plasma levels in the TT group were significantly higher than those in the CC and CT groups. Moreover, we observed that the severity of white matter lesions was associated with women and positively correlated with age, previous coronary heart disease, luminal infarction, and MTHFR polymorphism. The multivariate logistic regression analysis showed that age, TT genotype, and lacunar infarction were independent risk factors for white matter hyperintensity (WMH). Importantly, we showed that there was a significant correlation between Hcy plasma levels and MTHFR gene polymorphism, with the TT genotype constituting an independent risk factor for WMH. Therefore, we recommended early detection of MTHFR gene polymorphisms with concomitant early intervention concerning risk factors to delay the occurrence of cognitive impairment in CSVD elderly patients.

Association of MTHFR gene polymorphism C677T (rs1801133) studies with early primary knee osteoarthritis in a South Indian population: a hospital-based study.

Osteoarthritis (OA) is the most commonly occurring disease of middle and elderly population, which is characterized by focal loss of joint articular cartilage, osteophyte formation and sub chondral bone remodeling. Classical risk factors of OA include age, gender, weight, joint injury, trauma, however hereditary component is one of the main crucial factors. Several genome wide association studies and candidate gene approaches have identified genetic variants involved in the influence and association of OA. In the current study influence of Methylene tetra hydro folate reductase MTHFR C677T (rs1801133) gene with early primary knee OA was evaluated. In this study 400 samples were included (200 cases & 200 controls). DNA was extracted & processed for PCR- RFLP evaluation and genotype analysis. Statistical analysis was performed & results indicated a lack of association between MTHFR gene polymorphism and early primary KOA. The stratification was done based on age & gender and also both. Individual's i.e females below the age of 40 years are more prone to the disease when compared with males. MTHFR gene polymorphism showed a lack of association with early primary knee osteoarthritis. To the best of our knowledge this is the first study from south India.

MTHFR Gene-Polymorphism and Infertile Men in Indian Population: A Systematic Literature Review.

Single nucleotide polymorphisms (SNPs) in the genetic makeup of the methylenetetrahydrofolate reductase gene (MTHFR C677-T, A1298-C, and G1793-A) alongside environmental and lifestyle component has shown some links as a potential factor responsible for male infertility across the globe posing huge genetic vulnerability to the gender. However, SNPs in the MTHFR gene implicated in male infertility are not without their own controversial results even within the same population. The goal of this study was to provide comprehensive insights into the controversial nature of MTHFR gene polymorphism on male infertility across all Indian populations as well as other ethnicities. The electronic PubMed database was utilized to conduct and select eligible studies for this systematic review (update to December 2021). Only high-quality studies with a link between MTHFR polymorphisms and male infertility were included based on our exclusion and inclusion criteria. The connection between the MTHFR gene polymorphism and male infertility in Indian population studies was evaluated using odds ratios (ORs) with a 95% confidence interval (CI). A total of five studies presenting 1,237 cases and 1,044 controls were assessed for this study. The collective results revealed that MTHFR C667-T and A1298-C gene polymorphism were significantly linked with an increased chance of male infertility both in south India and north India, however, with some conflicting results. Interestingly, no study has been carried out to investigate the impact of G1793-A polymorphism on infertile males in the Indian population at the time of our report. Results generated from the few case-control evaluated on MTHFR gene polymorphism in the Indian population are found to conflict with some extrinsic factors (such as nutritional status-folate metabolism, lifestyle, varying recruitment procedures, and epigenetic elements) identified to have played some critical roles. Therefore, broader studies across all regions in India addressing the grave impact of MTHFR gene polymorphism on male infertility are of utmost importance.

Lower plasma glutathione, choline, and betaine concentrations are associated with fatty liver in postmenopausal women.

Postmenopausal women are at high risk of hepatic steatosis, which may be associated one-carbon metabolism (OCM) abnormalities. We hypothesized that lower folate, choline, betaine, and glutathione (GSH) concentrations but higher total homocysteine and trimethylamine N-oxide concentrations are associated with fatty liver (FL) in postmenopausal women. We aimed to identify relationships between OCM and nonalcoholic fatty liver disease biomarkers in postmenopausal women. A total of 131 postmenopausal women participated in this study and were stratified by the incidence of FL based on the hepatic steatosis index (HSI). Food intake was evaluated using dietary records. Aspartate aminotransferase and alanine aminotransferase concentrations in serum were measured using the colorimetric method. Total homocysteine and GSH concentrations in plasma were measured using high-performance liquid chromatography. Folate and phosphatidylcholine (PC) concentrations were determined in red blood cells using an enzyme-linked immunosorbent assay. Other OCM biomarkers concentrations were measured using the isotope dilution analysis. Women with FL (HSI > 36) had lower GSH, choline, and betaine concentrations than women without FL (HSI < 36). Higher HSI level was negatively correlated with betaine and PC and positively correlated with plasma choline/betaine ratio. Lower GSH and higher carnitine concentrations in the blood are associated with an increased risk of FL. MTHFR (rs180130) T-allele carriers had lower levels of GSH than the CC homozygotes. Postmenopausal women with FL have lower GSH, choline, and betaine concentrations, which may play a role in fat accumulation in the liver. It seems important to consider the dietary intakes of these nutrients in postmenopausal women.

A Study of the MTHFR Gene Prevalence in a Rural Tennessee Opioid Use Disorder Treatment Center Population.

Background: Opioid Use Disorder (OUD) has been linked to dopamine and the neurological reward centers. Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in the production of many neurotransmitters such as dopamine. As such, MTHFR variants that lead to decreased production of neurotransmitters may play a role in OUD. However, lacunae exist for characterizing the prevalence of the MTHFR mutations in an OUD population. The objective of this study was to determine prevalence of the MTHFR gene mutations in a rural Tennessean population with OUD. Methods: This study was a retrospective cohort of individuals with OUD that evaluated the prevalence of MTHFR variants. Patients were categorized as normal, homozygous C677T, heterozygous C677T, homozygous A1298C, or heterozygous A1298C. The primary outcome was a qualitative comparison of the prevalence of each of the MTHFR variants in our cohort to the publicly reported MTHR polymorphism prevalence. Secondary outcomes include race and ethnicity differences as well as stimulant use differences for each of the variants. Results: A total of 232 patients undergoing care for opioid use disorder were included in the study. Of those included, 30 patients had a normal MTHFR allele and 202 had a variant MTHFR allele. Overall, the prevalence of any MTHFR variant was 87.1% (95% CI 82.6-91.4%). When comparing those with a normal MTHFR allele to those with any MTHFR variant, there was no difference in age, sex, race and ethnicity, or stimulant use. Conclusion: The overall prevalence of MTHFR variants in patients with opioid use disorders is high.

Effect of interaction between occupational stress and polymorphisms of MTHFR gene and SELE gene on hypertension.

BACKGROUND: Gene-environment interaction is related to the prevalence of hypertension, but the impact of genetic polymorphisms on hypertension may vary due to different geography and population. OBJECTIVE: To explore the impact of the interaction among occupational stress and MTHFR gene and SELE gene polymorphism on the prevalence of hypertension in Xinjiang oil workers. METHODS: A case-control study was conducted on 310 oil workers. In an oilfield base in Karamay City, Xinjiang, 155 hypertensive patients aged 18~60 years old with more than one year of service were selected as the case group, and 155 oil workers without hypertension were selected as the control group according to the 1:1 matching principle (matching conditions: the gender and shift were the same. The age is around 2 years old). The Occupational Stress Scale was used to evaluate the degree of occupational stress, PCR technique was used to detect MTHFR and SELE gene polymorphism, Logistic regression analysis was used to analyze the effects of gene and occupational stress on hypertension, and gene-gene and gene-environment interactions were analyzed by generalized multi-factor dimension reduction method. RESULTS: The G98T polymorphism of SELE gene (χ2 = 6.776, P = 0.034), the C677T (χ2 = 7.130, P = 0.028) and A1298C (χ2 = 12.036, P = 0.002) loci of MTHFR gene and the degree of occupational stress (χ2 = 11.921, P = 0.003) were significantly different between the case group and the control group. The genotypes GT at the G98T polymorphism of the SELE gene (OR = 2.151, 95% CI [1.227-3.375]), and the dominant model (AC/CC vs AA, OR = 1.925, 95% CI [1.613-3.816]); AC and CC at the A1298C polymorphism of the MTHFR gene (OR AC = 1.917, 95% CI [1.064-3.453]; OR CC = 2.233, 95% CI [1.082-4.609]), the additive model (CC vs AA, OR = 2.497, 95% CI [1.277-4.883]) and the dominant model (AC/CC vs AA, OR = 2.012, 95% CI [1.200-3.373]); at the C677T polymorphism of the MTHFR gene CT and TT (OR CT = 1.913, 95% CI [1.085-3.375]; OR TT = 3.117, 95% CI [1.430-6.795]), the additive model (CC vs AA, OR = 1.913, 95% CI [1.085-3.375]) and the dominant model (AC/CC vs AA, OR = 2.012, 95% CI [1.200-3.373]), which could increase hypertension risk (P < 0.05). The gene-gene interaction showed that there was a positive interaction between the A1298C and C677T sites of the MTHFR gene, and the gene-occupational stress interaction showed that there was a positive interaction between the A1298C and C677T sites of the MTHFR gene and the occupational stress. CONCLUSION: The interaction of gene mutation and occupational stress in Xinjiang oil workers maybe increase the risk of hypertension.

Association of the methylenetetrahydrofolate reductase (MTHFR) gene variant C677T with serum homocysteine levels and the severity of ischaemic stroke: a case-control study in the southwest of China.

OBJECTIVE: To determine whether the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism is linked to the risk of ischaemic stroke and circulating homocysteine (Hcy) levels in a Chinese population. METHODS: This case-control study recruited angiogram-diagnosed patients with ischaemic stroke and healthy control subjects. The plasma Hcy concentrations were measured and the MTHFR C677T gene polymorphism was genotyped. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of the ischaemic stroke. RESULTS: This study recruited 198 patients with ischaemic stroke and 168 controls. The TT genotype conferred a higher risk for ischaemic stroke than the CC genotype (odds ratio of 3.563; 95% confidence interval [CI] 1.412, 4.350). The T allele was the predisposing allele for ischaemic stroke. Hcy had an area under the receiver operating characteristic (ROC) curve of 0.624 (95% CI 0.530, 0.758). The ROC for Hcy demonstrated its usefulness in predicting ischaemic stroke. Hcy levels were not associated with ischaemic stroke severity as measured by the NIHSS. CONCLUSION: The MTHFR C677T gene polymorphism affects circulating Hcy levels. The MTHFR C677T gene polymorphism and hyperhomocysteinaemia may play important roles in predicting the risk of ischaemic stroke.