Association Of Methylenetetrahydrofolate Reductase Research Articles

Association of Methylenetetrahydrofolate Reductase (MTHFR) Polymorphism with Osteosarcoma in a Mexican Population

The methylenetetrahydrofolate reductase (MTHFR) gene 677CàT polymorphism is capable of altering folate metabolism and can modify certain neoplasia risk. Reports have suggested that folate can have an influence on bone development and so it is of interest to know if the MTHFR 677CàT polymorphism is associated with the malignant transformation process of this tissue. The polymorphism was determined in 55 patients with osteosarcoma and in 180 healthy individuals. Compared with C/T+C/C genotypes, a 3.7-fold reduction in osteosarcoma probability is possible with the T/T genotype (OR 0.27, CI 95% 0.07–0.82). Undoubtedly, further studies, utilizing large samples and carried out on different populations, are necessary to confirm these results.

Association of methylenetetrahydrofolate reductase gene variant C677T and folate levels in non-syndromic cleft lip/palate among Sindhi, Pakistani population.

The object ives of this study were to determine the association of methylenetetrahydrofolate reduc tase (MTHFR) gene variant C67 7 T with non -syndromic cl eft lip/palate (NSCLP) in Pakistani population and compare the m aternal serum foli c acid levels in NSCLP-affected and healthy group. A c om parative cross sec ti onal study was conducted between 2017 and 2019 at Liaquat U niversity of Medi cal and Health Science s, Jamshoro. Sixty motherinfant dy ads were recruited (n=120), inc luding NSCLP-affected and healthy infants alo ng with t heir mother s. The MTHFR C677T vari ant exhibited si gnificant association with NSCLP in dominant and over-domi nant models. No differences in maternal serum folic acid levels were obse rved between both th e groups; however, the folic acid intake during pre-conception period was associated w ith decreased risk for NSC LP. Our stu dy suggested that MTHFR 677 CT genotype was related with decreased risk for NSCLP in Sindhi, Pakistani, population. Pre -conception folic acid may decrease the ri sk for ora l clefts.

Association of Methylenetetrahydrofolate Reductase (MTHFR) Gene C677T (rs1801133) polymorphism among Sudanese patients with chronic myelogenous leukemia

Association of Methylenetetrahydrofolate Reductase (MTHFR) Gene C677T (rs1801133) polymorphism among Sudanese patients with chronic myelogenous leukemia

Association of Methylenetetrahydrofolate Reductase (MTHFR) Gene C677T (rs1801133) polymorphism among Sudanese patients with chronic myelogenous leukemia

Background: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating the intracellular folate metabolism which plays an important role in carcinogenesis through DNA methylation. Objectives: The current study aimed to determine the association between MTHFR C677T polymorphisms and the risks of chronic myeloid leukemia (CML). Material and methods: This are hospital based cross sectional case control study, a total of 170 Sudanese subjects were enrolled, and 75 patients with chronic myeloid leukemia and 75 age- and sex matched healthy volunteers as a control group. Genomic DNA was extracted by sodium chloride method and The SNPs genotypes were determined using polymerase chain reaction followed by restriction fragment length polymorphism method. (PCR- RFLP). Data of this study were collected using a structured interview questionnaire and analyzed by statistical package for social sciences (version 21). Results: The frequency of the CC genotype was higher in the control group compared with patients (100%,96%), while of the CT genotype was higher in the case (4%) than in control (0.0%); the TT genotype was absent in both study groups, the frequencies T and C allele were 0.02 and 0.98 in CML patient group and 0.00, 0.100 respectively in the control group. There was no clinically significant association between age (P.value= 0.3), gender (P.value= 0.4) and genotype, also there was no statistically significant association when compare case with control genotype (p. value 0.08). Conclusion: C677T MTHFR polymorphism is not associated with the risk of CML among the Sudanese population

Association of methylenetetrahydrofolate reductase (MTHFR) rs1801133 (677C>T) gene polymorphism with ischemic stroke risk in different populations: An updated meta-analysis.

Background: Recently, increasing evidence has implicated methylenetetrahydrofolate reductase (MTHFR) gene mutation as a risk factor for ischemic stroke (IS) in the general population. However, studies have been inconclusive and lack evidence on specific populations. We aim to determine whether the rs1801133 (NC_000001.11 (MTHFR):g. 677C>T (p.Ala222Val) variant, we termed as MTHFR rs1801133 (677C>T), is linked to an increased risk of IS in different age groups and ancestry groups. Methods: The literature relevant to our study was found by searching the PubMed, Cochrane Library, Web of Science, EMBASE, and CNKI databases. A random effect model analysis was used to calculate the pooled odds ratio (OR) and 95% confidence interval (CI) to evaluate any possible association. We conducted a subgroup analysis based on the age and ancestry groups of the included populations. Results: As of March 2022, 1,925 citations had been identified in electronic databases, of which 96 studies involving 34,814 subjects met our eligibility criteria. A strong link was found between IS and the MTHFR gene rs1801133 (677C>T) polymorphism in all genetic models [dominant genetic model (OR = 1.47; 95%CI = 1.33-1.61; p < 0.001), recessive genetic model (OR = 1.52; 95%CI = 1.36-1.71; p < 0.001), heterozygous model (OR = 1.36; 95%CI = 1.24-1.48; p < 0.001), homozygous model (OR = 1.82; 95%CI = 1.58-2.11; p < 0.001), and T allelic genetic model (OR = 1.37; 95%CI = 1.27-1.48; p < 0.001)]. Further subgroup analyses indicated that the MTHFR rs1801133 (677C>T) variant may increase the risk of IS in Asian, Hispanic, or Latin population, middle-aged, and elderly populations (p < 0.001). Conclusion: Our results implied that mutation of the T allele of MTHFR rs1801133 (677C>T) could be a risk factor for IS. A significant association was found among Asian, Hispanic, or Latin population, middle-aged, and elderly people.

Association of Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in breast cancer patients of Bihar: Case-control study

Breast cancer (BC) is the most frequent cancer in women globally and the main cause of cancer-related mortality. MTHFR C677T is a functional polymorphism in the genes encoding a one-carbon metabolism enzyme that affect folate metabolism and may be associated with breast cancer susceptibility. We have conducted a case-control study taking 100 cases of diagnosed breast cancer and 100 healthy control. PCR-RFLP technique was used to detect the genotype of C677T polymorphism in the study population.About 35% of cases had normal genotype(C677C), 49% had the genotype C677T &amp; rest 16% had the genotype T677T for MTHFR. Among control the frequency of C677C genotype was 55% C677T was 40% &amp; T677T was 5%. C677T &amp; T677T MTHFR genotype were more common in case as compared to control [χ2 (2, N = 200) = 11.12, p = 0.004]. T allele frequency was significantly higher in case (40%) as compared to control (5%) [χ2 (1, N = 400) = 10.91, p = 0.001]. Cases with MTHFR 677TT genotype had a significantly higher risk of BC than 677CC individual [OR=1.64 (1.03 to 2.10)] and increasing T-allele was significant in BC [OR=1.07 (0.71 to 1.33)] (P for trend = 0.04).C677T of MTHFR gene has a strong correlation with breast cancer in the studied population and can be used as a prognostic marker for the development of breast cancer.

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.

The association of MTHFR (rs1801133) with hypertension in an indigenous south African population.

Aims: The current study sought to investigate the association between the methylenetetrahydrofolate reductase (MTHFR) variant (rs1801133) and the risk of developing hypertension (HTN) in an indigenous South African population. Methods: A total of 442 participants (hypertensive, n = 279 and non-hypertensive, n = 163) from the indigenous tribe residing in Mthatha, Eastern Cape (South Africa) were recruited. HTN was defined as a systolic (SBP) and diastolic blood pressure (DBP) of ≥130/80 mmHg following American Heart Association guidelines. The genotyping of MTHFR (rs1801133) was assessed using MassARRAY® System. Thereafter, the association between rs1801133 in various genetic models and HTN was determined by logistic regression model analysis. Furthermore, the interaction between rs1801133 and selected risk factors on HTN was performed using the open-source multifactor dimensionality reduction (MDR). Results: The low frequency of the T allele (5%) was also observed when compared with the C allele (95%) in both cases and controls. After adjusting for confounding factors (gender, smoking status, BMI, and blood glucose levels), there were no significant associations were observed between rs1801133 and the risk of HTN in all genetic models: genotypic (OR 0.75, 95% CI 0.29–1.95, p = 0.56), dominant (OR 0.86, 95% CI 0.35–2.16, p = 0.75), co-dominant (OR 1.33, 95% CI 0.51–3.48, p = 0.55) and allelic (OR 0.80, 95% CI 0.49–1.62, p = 0.70) in logistic regression analysis. However, a significant interaction was reported among rs1801133, age, and gender (p < 0.0001) with the risk of HTN. Conclusion: The present study reports on the lack of association between MTHFR (rs1801133) and the risk of HTN in an indigenous South African tribe. However, an interaction between gender, age, and rs1801133 was observed. Thus, future studies with a large sample size are required to further validate these findings.

Association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with vitamin B12 deficiency and adverse perinatal outcomes among pregnant women of rural South India - a cross sectional longitudinal study.

To determine the occurrence of MTHFR gene polymorphisms and to study their association with vitamin B12 deficiency and adverse perinatal outcomes among a cohort of pregnant women from Kaniyambadi block, Tamil Nadu. 120 consecutive pregnant women who were ≤20weeks of gestational age from the 82 villages of Kaniyambadi block were recruited. Genomic DNA was isolated from the peripheral blood. PCR amplification was done followed by Sangers sequencing. Maternal and neonatal outcomes were extracted. Data was entered and analysed. Our study found the occurrence of c.1298A>C variant in homozygous state in 14.2% and c.677C>T heterozygous state in 15%. Sanger sequencing of exon 7 identified another pathogenic variant c.1262G>T in heterozygous state in two of them. Both the mothers who harboured that variant had preterm delivery and one of them gave birth to a low-birth-weight neonate. In the entire cohort, 5% of the mothers had abortion, 4.2% of them had preterm delivery and 8.8% of the neonates had low birth weight. Presence of c.1298A>C or c.677C>T variants were associated with vitamin B12 deficiency [Pearson Chi squared value (χ2)=7.9 and 7.6 respectively; p=0.02]. Heterozygous pathogenic variant c.1262G>T was associated with both adverse maternal [χ2=11.5; p=0.001] and neonatal [χ2=18.3; p=0.009] outcomes. MTHFR gene polymorphisms could be associated with several adverse perinatal outcomes and vitamin B12 deficiency. Further larger studies are needed toprove the pathogenicity of c.1262G>T variant on pregnancy.

Association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (C677T and A1298C) with thyroid dysfunction: A meta-analysis and trial sequential analysis.

Recent studies have shown that two common methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (C677T and A1298C) might correlate with thyroid dysfunction, but the results remain inconsistent. We carried out a meta-analysis aiming to assess the relationship of both polymorphisms with thyroid dysfunction. The PubMed, EMBASE, CNKI (China National Knowledge Infrastructure), CBMdisc (China Biology Medicine disc), WeiPu and Wanfang databases were searched up to September 2021. Case-control and cohort studies on MTHFR polymorphism and thyroid dysfunction were identified. Eight studies from six publications were finally included in our meta-analysis, including 817 patients and 566 controls. After pooled analysis, we found that the MTHFR C677T polymorphism was associated with an increased risk of hypothyroidism (TT vs. CC+CT/recessive model: OR = 2.07, 95% CI: 1.02-4.20, P = 0.04; TT vs. CC/homozygote model: OR = 2.35, 95% CI: 1.13-4.86, P = 0.02), while trial sequential analysis (TSA) revealed that it could be a false positive result. The MTHFR A1298C polymorphism was related to a decreased risk of hypothyroidism (C vs. A/allele model: OR = 0.63, 95% CI: 0.44-0.92, P = 0.02; CC vs. AC+AA/recessive model: OR = 0.42, 95% CI: 0.22-0.79, P = 0.007; CC vs. AA/homozygote model: OR = 0.43, 95% CI: 0.25-0.85, P = 0.02), which was conclusive according to TSA. The results of this meta-analysis suggest that MTHFR A1298C seems to be a protective factor for hypothyroidism, while the MTHFR C677T polymorphism may be a risk factor. However, more well-designed studies with larger sample sizes are needed to obtain more reliable results of the association between the MTHFR C677T polymorphism and hypothyroidism.

Association of MTHFR (rs 1801133) gene polymorphism with biochemical markers of B12 deficiency in type 2 diabetes mellitus patients on metformin therapy

BackgroundLong-term administration of metformin in Type 2 Diabetes mellitus (T2DM), interferes with the absorption of vitamin B12 resulting in deficiency. Low levels of vitamin B12 are associated with cardiovascular morbidity and mortality in T2DM patients. Several genetic variants are associated with vitamin B12 deficiency; one among them is Methylene Tetrahydrofolate reductase (MTHFR). We analyzed MTHFR (rs180133) polymorphism and its association with metformin induced vitamin B12 deficiency in T2DM patients. MethodsThree hundred T2DM patients were included. For the study and they were screened for vitamin B12 deficiency markers – Methyl malonic acid (MMA), Homocysteine (Hcy) and high sensitive C reactive protein (hsCRP). Genetic variant was analyzed by ARMS-PCR method. Data was analyzed with various statistical tools like ROC, Odds ratio and Likelihood ratio. ResultsThere is significant reduction in folic acid and vitamin B12 in metformin users. HsCRP, Hcy and MMA are significantly increased with P < 0.001 in patients with metformin induced B12 deficiency. T allele in MTHFR (T allele ORs =2.1, TT genotype =3.6) showed risk of vitamin B12 deficiency in T2DM patients on metformin therapy. MTHFR gene polymorphism of TT genotype had a Likelihood ratio (LR) of 2.46 for folic acid, 2.77 for MMA and 3.38 for Hcy. ConclusionWe found an association between MTHFR rs180133, 677C > T and vitamin B12 status in T2DM patients on metformin therapy. Folic acid, MMA and Hcy were found to have high specificity in concordance with MTHFR which showed to be a good predictor for vitamin B12 deficiency in T2DM patients on metformin therapy.

Association of methylenetetrahydrofolate reductase (MTHFR) and cystathionine β-synthase (CBS) genes promoter methylation pattern with the risk of essential hypertension

Methylenetetrahydrofolate reductase (MTHFR) and cystathionine β-synthase (CBS) are key enzymes in the metabolism of homocysteine pathway whose dysfunction can lead to essential hypertension (EH). This study aimed to investigate the possible association of MTHFR and CBS genes promoter methylation patterns with the risk of EH. We also aimed to search differentially expressed microRNAs (miRs) and demonstrate the role of miRs in the aberrant DNA methylation in essential hypertensive patients by targeting DNA methyltransferases (DNMTs).20 essential hypertensive patients and 20 healthy controls were selected. DNA methylation levels of 10 CpG dinucleotides on MTHFR and 19 CpG dinucleotides on CBS genes promoter was measured using Bisulfite-Sequencing PCR (BSP). The GSE118578 profile was downloaded from the GEO database to identify differentially expressed miRs in hypertensive patients and R statistical software was used to analyze the data. Enrichment analysis was conducted to predict target genes using databases of Targetscan, and miRDB-MicroRNA Target Prediction Database.No significant association between MTHFR gene methylation and EH was observed. There was a significant association between one of the CpG sites of CBS gene promoter (CpG19 (+1035C)) and EH [OR = 5.3(0.895–31.393), p = 0.047]. Furthermore, we reported a list of miRs that may have an essential role in regulating DNA methylation by targeting DNMTs.Our findings showed that hypermethylation of CpG19 (+1035C) of CBS gene promoter could increase the risk of EH. Methylation status of MTHFR gene had no significant association with EH. Also, in-silico investigation showed that miRs may affect aberrant genes methylation through altering DNMTs biogenesis.

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

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

Association of methylenetetrahydrofolate reductase (MTHFR) variant C677T and risk of carotid atherosclerosis: a cross-sectional analysis of 730 Chinese Han adults in Chongqing

BackgroundUncertainty still remains on the correlation of methylenetetrahydrofolate reductase (MTHFR) variant C677T with risk of carotid atherosclerosis (CAS), and there is a lack of reports on C677T/MTHFR in the Asian population. The association of C677T/MTHFR polymorphisms with CAS in the Chinese Han population in Chongqing was investigated in the present study.MethodsSubjects (n = 730, 214 females and 516 males, Han ethnicity) who provided an informed consent were randomly selected from the general population of Chongqing, China. Polymerase chain reaction-restriction fragment length polymorphism and Sanger sequencing genotyping assays were used to determine the MTHFR genotypes. The atherosclerosis index of the intima-media thickness (IMT) was measured by high-resolution ultrasound to evaluate the CAS. Less than 1.0 mm was considered as normal for IMT, 1.0–1.5 mm was considered as thickening, and ≥ 1.5 mm and a local bulge thickened in the lumen was considered as CAS. According to the carotid ultrasonography results, these subjects were divided into two groups: CAS-group (IMT ≥ 1.0 mm) and control group (IMT < 1.0 mm).ResultsThe frequency of C/T heterozygotes, T/T homozygotes genotype was significantly higher in the subjects with CAS (62% vs. 36.9%; 16.2% vs. 9.5%; 47.2% vs. 27.9%, P < 0.05), while the frequency of C/C homozygotes and C allele was significantly lower (21.8% vs. 53.7%; 52.8% vs. 72.1%, P < 0.05), when compared to the control group. The risk of CAS was higher for subjects with C/T heterozygotes and T/T homozygotes (OR = 4.06, 95% CI: 2.76–5.98, P < 0.001 and OR = 3.14, 95% CI: 1.73–5.69, P < 0.001, respectively), when compared to the subjects with the C/C genotype. In the model 1 (CT + TT versus CC), C677T/MTHFR was significantly associated with the prevalence of CAS, and the all adjusted OR values for CAS were 3.87 (95% CI, 2.67 to 5.62) in all, 17.18 (95% CI, 7.27 to 40.49) in women and 2.57 (95% CI, 1.65 to 3.99) in men after adjusting for potential confounding factors.ConclusionsThe present study suggests that a mutation in the methylenetetrahydrofolate reductase gene is a risk factor of CAS in the Chinese Han population.

Association of Methylenetetrahydrofolate Reductase (MTHFR) (C677T) gene polymorphism with Breast Cancer in Egyptian women.

Association of Methylenetetrahydrofolate Reductase (MTHFR) (C677T) gene polymorphism with Breast Cancer in Egyptian women.

Association of MTHFR, IL-6 and ICAM-1 gene Polymorphisms with Coronary Artery Disease in South-Indian Ethnic Subset: A Case-Control Study

Introduction: Cardiovascular disease is the leading cause of mortality and morbidity all over the world. Among these cardiovascular deaths, half result from coronary artery disease (CAD). Increased prevalence of CAD is associated with increased levels of inflammatory markers. Phenotypic variations of these markers may depend on physiological stress or genetic variations. Materials and Methods: Single nucleotide polymorphism analysis of methylenetetrahydrofolate reductase (MTHFR), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) genes was done by PCR-DNA sequencing method. Results: Statistically significant elevation of inflammatory markers- homocysteine, hsCRP and fibrinogen were found in CAD group (p≤0.05). Multiple sequence alignment showed a single nucleotide mutation i.e., c.677 C>T (p. A222V) in exon-4 of MTHFR in 10% of CAD group and was associated with an increased risk of CAD (OR: 12.21). Mutations observed in exon-4 of IL-6 gene (in 26% of cases) was significantly associated with an increased risk of CAD (OR: 36.36). ICAM-1 (exon-6) mutation i.e., c.1405 A>G (p. K469E) was observed in 18% of patients and an increased risk of CAD (OR: 23.12). Conclusion: Polymorphisms observed in MTHFR, IL-6 and ICAM-1 genes in South- Indian ethnic population which are associated with elevated levels of inflammatory markers – homocysteine, hsCRP and fibrinogen appear to be predisposing factors for atherosclerosis.

Association of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms with coronary artery disease (CAD) in a North Indian population

There is significant variation in reported associations of the MTHFR C677T (rs1801133) and A1298C (rs1801131) polymorphisms and coronary artery disease (CAD) in different global populations. This study aims to identify any individual or combined associations between the 1298 and 677 loci of MTHFR and CAD in a North Indian population. A total of 159 patients and 166 controls were genotyped using validated TaqMan assays. Odds ratio analysis identified associations at crude level and multiple logistic regression controlled for confounding variables. Linkage disequilibrium between the loci was assessed along with haplotype association analysis. At the C677T locus, homozygosity of the T allele identified a significantly protective association (OR = 0.38, CI: 0.24–0.60). For the A1298C locus the AC genotype had a protective effect in codominant model (OR = 0.53, CI: 0.32–0.85) and CC genotype showed a susceptible association in recessive model when controlled for age, sex and lipids (OR = 2.70, CI: 1.27–5.77). This study identified that, independently, both heterozygous genotypes show a protective association with CAD. In addition the CC genotype of A1298C in recessive model was a susceptible genotype. The combined associations of MTHFR are protective (primarily due to the effects of C677T locus) suggesting an interaction between the loci and their associations with CAD within this sample.

(Association of Methylenetetrahydrofolate Reductase (MTHFR) A1298C gene polymorphism with Breast Cancer in Egyptian women)

(Association of Methylenetetrahydrofolate Reductase (MTHFR) A1298C gene polymorphism with Breast Cancer in Egyptian women)

Methylenetetrahydrofolate reductase C677T and methionine synthase A2756G gene polymorphisms and associated risk of cardiovascular diseases: A study from Jammu region

AimPotent risk factors at both genetic and non-genetic levels are accountable for susceptibility and instigation of different cardiovascular phenotypes. Recently, homocysteine is being identified as an important predictor for cardiovascular diseases. Homocysteine remethylation plays a key role in the synthesis of methionine and S-adenosine methionine. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) genes are known to regulate the homocysteine remethylation reaction and higher homocysteine level is significantly associated with diverse cardiovascular phenotypes. In this context, we aimed to carry out a study on the association of MTHFR (C677T) and MTR (A2756G) gene polymorphism with CVD in population of Jammu region of J&K state. Materials and methodsA total of 435 individuals were enrolled (195 CVD patients and 240 controls) for the case–control study. Genotyping of MTHFR C677T and MTR A2756G gene polymorphism was done by PCR-RFLP technique. Biochemical parameters were estimated by biochemical analyser. ResultsMetabolic variables such as serum LDL-C, TC and TG were significantly higher in patients (p<0.0001), whereas serum HDL-C was higher in controls. Majority of the patients were having history of hypertension (57.44%; p<0.0001) as a concomitant condition. The evaluation of genetic association showed that, MTHFR C6877T (OR: 8.89, 95% CI: 2.01–39.40) and MTR A2756G (OR: 1.48, 95% CI: 1.09–2.00) polymorphisms associated with higher risk of CVD. ConclusionThe present study reveals significant differences in nongenetic variables among patients and control as well as association of gene polymorphisms with CVD risk.

Association of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with autism: evidence of genetic susceptibility.

Autism (MIM 209850) is a heterogeneous neurodevelopmental disease that manifests within the first 3years of life. Numerous articles reported that dysfunctional folate-methionine pathway enzymes may play an important role in the pathophysiology of autism. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme of this pathway and MTHFR C677T polymorphism reported as risk factor for autism in several case control studies. However, controversial reports were also published. Hence the present meta-analysis was designed to investigate the relationship of the MTHFR C677T polymorphism with the risk of autism. Electronic databases were searched for case control studies with following search terms - 'MTHFR', 'C677T', in combination with 'Autism'. Pooled OR with its corresponding 95% CI was calculated and used as association measure to investigate the association between MTHFR C677T polymorphism and risk of autism. Total of thirteen studies were found suitable for the inclusion in the present meta-analysis, which comprises 1978 cases and 7257 controls. Meta-analysis using all four genetic models showed significant association between C677T polymorphism and autism (ORTvs.C=1.48; 95% CI: 1.18-1.86; P=0.0007; ORTT + CT vs. CC=1.70, 95% CI=0.96-2.9, p=0.05; ORTT vs. CC=1.84, 95% CI=1.12-3.02, p=0.02; ORCT vs.CC=1.60, 95% CI=1.2-2.1, p=0.003; ORTT vs.CT+CC=1.5, 95% CI=1.02-2.2, p=0.03). In total 13 studies, 9 studies were from Caucasian population and 4 studies were from Asian population. The association between C677T polymorphism and autism was significant in Caucasian (ORTvs.C=1.43; 95% CI=1.1-1.87; p=0.009) and Asian population (ORTvs.C=1.68; 95% CI=1.02-2.77; p=0.04) using allele contrast model. In conclusion, present meta-analysis strongly suggested a significant association of the MTHFR C677T polymorphism with autism.