677T Allele Research Articles

Associations of Genetic Variants of Methylenetetrahydrofolate Reductase and Serum Folate Levels with Metabolic Parameters in Patients with Schizophrenia.

The one-carbon metabolism pathway is a suitable candidate for studying the genetic and epigenetic factors contributing to metabolic abnormalities in patients with schizophrenia. We recruited 232 patients with schizophrenia and analyzed their serum folate, vitamin B12, and homocysteine levels and metabolic parameters to investigate the associations of genetic variants of methylenetetrahydrofolate reductase (MTHFR) and folate levels with metabolic parameters. MTHFR C677T and MTHFR A1298C were genotyped. Results showed that MTHFR 677T allele carriers had lower levels of total cholesterol and low-density lipoprotein cholesterol than those with the 677CC genotype. Metabolic parameters did not differ between MTHFR 1298C and 1298AA carriers. Patients with a low folate level had a lower high-density lipoprotein cholesterol level than those with a normal folate level, but the effect disappeared after adjustment for age, sex, and types of antipsychotics used. We found significant interactions between MTHFR A1298C and the folate level status (low vs. normal) in terms of body mass index and waist circumference. In conclusion, genetic variants in one-carbon metabolism might play a role in antipsychotic-induced metabolic abnormalities. Prospective studies on drug-naïve, first-episode patients with schizophrenia are warranted to identify key regions of DNA methylation changes accounting for antipsychotic-induced metabolic abnormalities.

Pathomorphology of gravid endometrium in patients with recurrent miscarriage in early periods with underlying chronic endometritis and the presence of low-functional alleles in folate cycle genes

AIM: This study aimed to identify the peculiarities of pathomorphological alterations in the gravid endometrium and polymorphism of the folate cycle genes in female patients with recurrent early miscarriage and underlying chronic endometritis.
 MATERIALS AND METHODS: The uterine mucosa of women who had uncomplicated pregnancies and decided to have an artifactual abortion within 512 weeks (control group, n = 36) and patients with recurrent miscarriage with underlying chronic endometritis (main group, n = 83) was histologically examined. The polymorphism of the folate cycle genes MTHFR С677Т (rs 1801133), MTHFR A1298C (rs 1801131), and MTRR A66G (rs 1801394) was studied in the female patients of the main group and women with the preserved reproductive function (comparison group, n = 52) through real-time polymerase chain reaction (PCR).
 RESULTS: Fibroblast-like cells (FLCs) of the stroma sequentially differentiated into predecidual cells from 5 weeks to 12 weeks of uncomplicated pregnancy. In the case of recurrent miscarriage against background chronic endometritis, defect was observed in the differentiation of FLCs of the endometrial stroma. This finding was associated with a decrease in the morphometric parameters of the cells and an increase in the frequency of the occurrence of the low-functional allele 677T in the methylenetetrahydrofolate reductase gene.
 CONCLUSION: The course and outcome of pregnancy in the first trimester were negatively affected by the structural inadequacy of endometrial stromal cells in recurrent miscarriage and chronic endometritis combined with the presence of the MTHFR 677T allele in a womans genotype.

Polyphenol-Rich Aronia melanocarpa Juice Consumption Affects LINE-1 DNA Methylation in Peripheral Blood Leukocytes in Dyslipidemic Women.

Cardiovascular disease (CVD) is associated with alterations in DNA methylation and polyunsaturated fatty acid (PUFA) profile, both modulated by dietary polyphenols. The present parallel, placebo-controlled study (part of the original clinical study registered as NCT02800967 at www.clinicaltrials.gov) aimed to determine the impact of 4-week daily consumption of polyphenol-rich Aronia melanocarpa juice (AMJ) treatment on Long Interspersed Nucleotide Element-1 (LINE-1) methylation in peripheral blood leukocytes and on plasma PUFAs, in subjects (n = 54, age range of 40.2 ± 6.7 years) at moderate CVD risk, including an increased body mass index, central obesity, high normal blood pressure, and/or dyslipidemia. The goal was also to examine whether factors known to affect DNA methylation (folate intake levels, MTHFR C677T gene variant, anthropometric and metabolic parameters) modulated the LINE-1 methylation levels upon the consumption of polyphenol-rich aronia juice. Experimental analysis of LINE-1 methylation was done by MethyLight method. MTHFR C677T genotypes were determined by the polymerase chain reaction–restriction fragment length polymorphism method, and folate intake was assessed by processing the data from the food frequency questionnaire. PUFAs were measured by gas–liquid chromatography, and serum lipid profile was determined by using Roche Diagnostics kits. The statistical analyses were performed using Statistica software package. In the comparison after vs. before the treatment period, in dyslipidemic women (n = 22), we observed significant decreases in LINE-1 methylation levels (97.54 ± 1.50 vs. 98.39 ± 0.86%, respectively; P = 0.01) and arachidonic acid/eicosapentaenoic acid ratio [29.17 ± 15.21 vs. 38.42 (25.96–89.58), respectively; P = 0.02]. The change (after vs. before treatment) in LINE-1 methylation directly correlated with the presence of MTHFR 677T allele, average daily folate intake, and the change in serum low-density lipoprotein cholesterol but inversely correlated with the change in serum triacylglycerols (R = 0.72, R2 = 0.52, adjusted R2 = 0.36, P = 0.03). The current results imply potential cardioprotective effects of habitual polyphenol-rich aronia juice consumption achieved through the modifications of DNA methylation pattern and PUFAs in subjects at CVD risk, which should be further confirmed. Hence, the precision nutrition-driven modulations of both DNA methylation and PUFA profile may become targets for new approaches in the prevention of CVD.

Homocysteine, vitamin B status and MTHFR polymorphisms in Italian infertile women

ObjectiveThe purpose of this study was to evaluate the vitamin B status related to the homocysteine pathway and the prevalence of polymorphisms of the MTHFR gene in infertile women programming homologous or heterologous ART. Study designWe investigated 393 consecutive Caucasian women, referred to the Internal Medicine Clinic at the Center for Assisted Reproductive Technology, in order to be framed for their vascular risk before starting homologous or heterologous (oocyte donation) procedures. Total homocysteine, Vitamin B12, folate and vitamin B6 were measured. The women were divided into quartiles of serum concentration of folate, vitamin B12 and vitamin B6. The C677T and A1298C polymorphisms of the MTHFR gene were genotyped by an electronic microchip technology. ResultsSixty-one women (15.5%) had hyperhomocysteinemia, 22.9% had reduced levels of vitamin B12, 4.1% had reduced levels of serum folate and 0.1% had a deficiency of vitamin B6. Women in the highest quartile of vitamin B12 and folates had lower homocysteine ​​levels than women in the first and second quartiles (p < 0.0001). The homozygosity for MTHFR C677T polymorphism was detected in 33.3% (131), and heterozygosity for MTHFR C677T polymorphism in 45.3% (178) of women. We observed a significant association between hyperhomocysteinemia and 677T allele, but not 1298C, of the MTHFR polymorphisms (p = 0.04). ConclusionsWe found inadequate vitamin B status related to the homocysteine ​​pathway in women planning Assisted Reproductive Technology. Moreover, interesting association was found regarding hyperhomocysteinemia in women carrying T allele of the C677T MTHFR polymorphism. A specific supplementation with 5-MTHF and adequate vitamin B12 concentrations before Assisted Reproductive Technology warrant serious consideration, in particular in women carrying T allele of the C677T MTHFR polymorphism.

The association between 5, 10 - methylenetetrahydrofolate reductase and the risk of unexplained recurrent pregnancy loss in China: A Meta-analysis.

Backgroud:To analyze the correlation between gene polymorphisms of 5,10- methylenetetrahydrofolate reductase (MTHFR) and risk of unexplained recurrent pregnancy loss (URPL) in Chinese women.Methods:Eligible studies were searched in Pubmed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure (CNKI) databases. Established inclusion criteria were used to screening articles, subsequently evaluate the quality of the included studies, Stata 16.0 PM and RevMan 5.3 software were conducted for meta-analysis. The pooled odds ratio (OR) with 95% confidence interval (CI) was determined to assess the relationship between MTHFR and risk of URPL in Chinese women.Results:For MTHFR C677T, fifty studies were included, involving 6677 URPL cases and 8111 controls. The overall results showed that MTHFR C677T was significantly correlated with URPL risk, especially in the homozygous model (TT vs CC; OR 3.06; 95% CI 2.56–3.66). For MTHFR A1298C, twenty-first studies were included, involving 3439 URPL cases and 3155 controls. The results showed that MTHFR A1298C was also significantly correlated with URPL risk in recessive (CC vs AC + AA; OR 1.55; 95% CI 1.25–1.93) and homozygous (CC vs AA; OR 1.53; 95% CI 1.22–1.91) models. In addition, sub-group results showed that no significant difference between north and south China populations in the MTHFR gene polymorphisms and URPL risk. Of note, the patients carrying MTHFR C677T and MTHFR A1298C joint mutants had no synergistic effect (OR 2.71; 95% CI 0.84–8.70) on the occurrence of URPL compared with the wild-type homozygous genotype (MTHFR 677CC/ MTHFR 1298AA).Conclusion:Studies included in this meta-analysis suggested that MTHFR 677T allele and 677TT genotype and MTHFR 1298CC genotype were both associated with URPL; testing MTHFR C677T gene polymorphism was a more appropriate target compared with other mutations in the prediction of URPL.

ASSOCIATION BETWEEN TUMOR NECROSIS FACTOR, BRAIN NATRIURETIC PEPTIDE AND POLYMORPHISM OF THE M235T OF THE ATG GENE IN HYPERTENSIVE PATIENTS WITH HEART FAILURE

Objective: To investigate the association between tumor necrosis factor alfa (TNFa), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and polymorphism of the M235T of the ATG gene in hypertensive patients with heart failure with preserved ejection fraction (HFpEF). Design and method: The main group of eighty-four patients (51 females and 33 males; mean age 62,7 ± 8,0 years) with HFpEF and arterial hypertension. Sixty-eight patients and eighteen healthy persons were carriers of 235T allele (MT+TT genotypes), sixteen patients had MM genotype of M235T polymorphism of ATG, determined by using of polymerase chain reaction. Levels of NTproBNP and TNFa were determined by enzyme-linked immunosorbent assay (ELISA) using «NTproBNP-BEST-ELISA» (Russia) and «TNFa-ELISA-BEST» (Russia), respectively. All statistical tests were 2-tailed and p &lt; 0,05 was considered statistically significant and performed in Statistica 10.0. Results: The significant difference in the level of TNFa in hypertensive patients with HFpEF depending on the different genotypes of M235T polymorphism of ATG was not found. Although the serum NTproBNP level increased in patients with MT+TT genotypes compared with patients with MM genotype (Table 1). Conclusions: The presence of T allele of M235T polymorphism of ATG in hypertensive patients with HFpEF was independently associated with increased level of NTproBNP

TG12-T5-V470 haplotype in the CFTR gene is associated with non-obstructive azoospermia in Iranian infertile men

IntroductionRecent studies have shown that some variations and polymorphisms of CFTR gene can be involved in other types of infertility apart from CBAVD. In this study, we decided to survey the poly-T, TG repeats and M470V of the CFTR gene in infertile men with non-obstructive azoospermia in Iran. Material and methodThis case-control study was performed on 203 NOA patients and a control group (n = 200), the peripheral blood samples were collected in EDTA vacuum tubes. Then genomic DNA was extracted and PCR-sequencing was carried out on the 3′ ends of intron 8 CFTR gene to identify poly-T and TG repeats. Genotyping of M470V was carried out using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). ResultThe mean age of the infertile men and in control group was 31 ± 3.7, 30 ± 2.6 years, respectively. Frequency of T5 allele in males with non-obstructive azoospermia was found higher than that of the control group (OR 2.5798, 95% CI 1.3013–5.1143, P < 0.001). The allelic frequency of TG12-5T in males with non-obstructive azoospermia was significantly higher than that observed in the control group (OR 15.7143, 95% CI 2.7576–89.5497, P < 0.001) and also the TG12-5T-V470 haplotype was significantly associated with NOA as compared to normal controls, (OR 19.2857, 95% CI 1.0458–355.6390, P < 0.0001). ConclusionIt seems that T5, TG12-T5 and also TG12-T5-V470 haplotype can be associated with the risk of NOA in men, but further researches are necessary to clarify accurate role CFTR gene in NOA.

Influence of Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphism on High-Dose Methotrexate-Related Toxicities in Pediatric Non-Hodgkin Lymphoma Patients.

PurposeThis retrospective study aimed to investigate the relationships between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C and high-dose methotrexate (HD-MTX)-related toxicities in pediatric non-Hodgkin lymphoma (NHL) patients.Patients and MethodsWe reviewed the medical records of 93 NHL patients aged under 18 years who received HD-MTX therapy at the dose of 5 g/m2 with 24-h infusion at Sun Yat-sen University Cancer Center between 2014 and 2019.ResultsThere were 61 males and 32 females, with a median age of 8.8 years (0.9–15.8 years). The tumor types included lymphoblastic lymphoma (n = 38), Burkitt’s lymphoma (n = 31), anaplastic large cell lymphoma (n = 18), diffuse large B-cell lymphoma (n = 6). Overall, 355 courses of HD-MTX therapy were prescribed. All patients were rescued with calcium folinate 12 h after the end of MTX infusion. We found that plasma MTX levels > 0.2 μmol/L at 48 h post-infusion increased the risk of developing oral mucositis (2.4% VS. 9.5%, P = 0.018). Also, patients carrying the C677T and T677T genotypes had tendencies to be more susceptible to oral mucositis (P = 0.034). Patients harboring mutant 677T allele were more likely to develop leucopenia (38.5 vs. 50.3%, P = 0.025) and thrombocytopenia (22.0 vs. 32.4%, P = 0.028). For polymorphism A1298C, the mutant genotype played a protective role in vomiting (11.1 vs. 4.3%, P = 0.018) but increased the risk of anemia (23.8 vs. 41.7%, P < 0.001) and leucopenia (38.1 vs. 50.3%, P = 0.021).ConclusionChildhood NHL patients harboring C677T genotype were more vulnerable to oral mucositis, leucopenia, and thrombocytopenia, while those with A1298C genotype were at a decreased risk of vomiting and more likely to develop anemia and leucopenia.

ENOS 894T allele can Contribute to Endothelial Dysfunction but not QT Interval Prolongation in Dialytic Patients

Background: Cardiovascular complications are common in chronic kidney disease (CKD) patients. Endothelial nitric oxide synthase (eNOS) is very important for the homeostasis of the cardiovascular system, and its gene polymorphism at position 894 (G&gt;T) has not been investigated with QTc interval in patients on dialysis. Objective: This study evaluated the association of the 894G&gt;T polymorphism with QTc prolongation and endothelial dysfunction risk in dialysis patients. Methods: Predialysis blood samples were collected for eNOS gene polymorphism, nitric oxide (NO), thiobarbituric acid reactive substances (TBARS), total antioxidant, asymmetric dimethylarginine (ADMA) and L-arginine, and 12-lead electrocardiograms were analyzed in these patients. Statistics were based on continuous and categorical variables using Fisher’s exact or Chi-square or one-way ANOVA or KruskalWallis tests. The results were considered significant when P &lt; 0.05. Results: The study showed that the GG genotype was prevalent, with 54% of patients, followed by 41% GT and 6% TT, and the genotypic distribution was not associated with QTc prolongation. Furthermore, patients with the T allele showed increased ADMA, L-arginine and peroxidation lipid levels with reduced NO synthesis. Conclusion: Our study showed a lack of association between QTc interval and eNOS polymorphism; however, it was found that patients with the T allele had a greater risk of developing endothelial dysfunction by ADMA, which could contribute to future cardiovascular complications and worsening of CKD.

Increased Risk of Clopidogrel-Induced Gastric Mucosal Erosion in Elderly Chinese Men Harboring the ABCB1 3435T Allele.

BackgroundIt is uncertain whether long-term use of clopidogrel alone can cause gastric mucosal injury. This study aimed to evaluate the relationship between ABCB1 C3435T polymorphisms, which could affect the intestinal absorption of clopidogrel, and gastric mucosal erosion in elderly Chinese men who used clopidogrel alone.MethodsWe selected 298 male patients (aged between 68.2 and 89.5 years, average age 78); 201 of them constituted the control group, and 97 constituted the case group. Patients taking clopidogrel alone who had undergone endoscopic screening for gastric erosion were analyzed for ABCB1 C3435T polymorphisms by a TaqMan assay.ResultsThe proportion of people carrying the ABCB1 3435T allele (n = 63, 64.9% vs n = 97, 48.3%, p = 0.007) was significantly higher in the case group than in the control group. After adjustments for significant factors were made, ABCB1 3435T allele carrier (OR 2.14, 95% CI 1.43–3.84, p <0.01) was found to be associated with gastric mucosal erosion in people who used clopidogrel alone.ConclusionCarrying the ABCB1 3435T allele may be a useful genetic predictor for clopidogrel-induced gastric mucosal erosion in elderly Chinese men.

Evaluation of progesterone and progesterone receptor gene PROGINS polymorphism in the development of some forms of premenstrual syndrome

One of the most common neuroendocrine syndromes in gynecology is premenstrual syndrome (PMS). The article is devoted to study of pro-gesterone level and frequency of polymorphic variants T1T2 of progesterone receptor gene PROGINS, as well as their possible relationship in patients with various forms of PMS. The object of the study were 50 women of reproductive age with diagnosis of PMS, including 25 women with edematous form of the disease, 25 – with neuropsychical form. Mild form of disease had 25 women, severe form – also 25 persons. Control group consisted of 25 women without diagnosis of PMS. Progesterone level was determined in blood serum twice in the first and second phase of menstrual cycle. Polymorphism T1T2 of progesterone gene receptor PROGINS was studied using polymerase chain reaction.We found hypoprogesteronemia of luteal phase of menstrual cycle in women with PMS, especially pronounced in persons with edematous and severe forms of the disease (p&lt;0.05).Polymorphic variant T1T2 of gene PROGINS can be considered as a marker of development of PMS. T1T1 genotype was significantly as-sociated with development of edematous form (χ2=4.50; р=0.03) and its presence may indicate a tendency to develop of severe form of PMS (χ2=3.21; р=0.07). T2 allele can be considered as a protective mechanism for the appearance of PMS, particularly its edematous and severe forms, in which the presence of T2 allele reduces the risk of PMS, respectively 3.0 times (χ2=4.50; p=0.03, OR=0.20 95% CI 0.05–0.78; p=0.02) and 1,71 times (χ2=3.21, p=0.07, OR=0.27, 95% CI 0.08–0.95, p=0.04) compared with control group. Reduced blood level of progesterone in women with PMS correlated with the presence of T1T1 genotype of gene PROGINS. By edematous, neuro-psychical, severe and mild forms of PMS and the presence of T1T1 genotype there were significantly low levels of this hormone in the second phase of menstrual cycle (p&lt;0.05) relative to women with the same genotype in the control group of. Furthermore, there was no statistically significant difference in progesterone level in women with T1T2 genotype in these groups compared with healthy women with same genotype (p&gt;0.05)

Gene polymorphism of blood coagulation factors and endothelial dysfunction in early and late preeclampsia.

The aim of our study was to find out the influence of gene polymorphisms of coagulation factors, endothelial dysfunction and regulators of blood pressure in early (EPE) and late preeclampsia (LPE). The study of genetic polymorphisms of blood coagulation factors and fibrinolysis (1691 G/A factor V Leiden (FVL), 20210 G/A prothrombin, -675 5G/4G PAI-1, 455 G/A fibrinogen β), endothelial dysfunction (192 Q → R paraoxonase 1, 677 C/T MTHFR, arterial pressure regulator (235 M/T angio­tensinogen II (AGT II)) using an PCR was performed. A prospective cohort study of 39 women with EPE, 93 with LPE and 44 pregnant women with a physiological pregnancy (C group) was conducted. The average gestational age at the time of delivery in EPE group was lower than in LPE and control group (p&lt;0.001). In group with EPE new-borns had low weight-growth characteristics, low grade by the Apgar scale and foetal distress (38.5% vs. 9.7%, p&lt;0.05). Caesarean section in EPE group was performed by 2.25 times more often than in control group and by 2,13 times than in LPE group (p&lt;0,05). It was detected that the number of 1691 GA FVL heterozygote carriers in the group with EPE was significantly higher than in LPE group (p&lt;0.05, OR=3.65, 95% CI 1.5-8.9) and control group (6.04, 1.7-21.6). The number of 20210 GG homozygotes and 20210 GA heterozygotes in prothrombin gene was probably lower in EPE group compared with the LPE and control group (0.03, 0.002-0.49, and 0.18, 0.06-0.53, respectively). It was established increase in frequency of 677 TT MTHFR genotype in EPE compared with control group (17.27; 0.9-317). Also, the carriers of 235T allele AGT II gene have an increased risk of EPE and PPE development (2.25, 1.2-4.2), (1.9, 1.1-3.3) respectively. The allele -455A of fibrinogen β gene increases the chances of developing EPE by 4.4 times (2.0-9.5), and LPE by 3.5 times (1.7-7.1). Risk factors that significantly increase the chances of developing early preeclampsia were identified: allele 1691 A of FV Leiden (5.96, 1.5-8.9), allele 20210 A of prothrombin (39.8, 2,3-679), 677T MTHFR (2.5, 1.18-5.3). In was detected that other researched polymorphisms between groups with PE were not significantly different and did not affect on time of preeclampsia development.

Methylene Tetrahydrofolate Reductase Gene Polymorphism C677T &amp; Risk of Type two Diabetes Mellitus in Beni-Suef Governorate

Background: Methylene Tetrahydrofolate Reductase (MTHFR) is known to be a regulatory enzyme of homocysteine metabolism. In many ethnic groups point mutations in MTHFR gene are implicated in the pathogenesis of diabetic nephropathy (DN) and other complications of type II diabetes mellitus (T2DM). Aim of the work: The aim of this study was to assess if MTHFR C677T gene polymorphism was one of the risk factors for the development of diabetic nephropathy as well as other complications in type 2 diabetes mellitus patients. Subjects and methods: The MTHFR C6777T polymorphisms were detected in 50 persons by PCR-RFLP. Subjects were divided into 2 groups; 30 patients with type II DM and 20 persons who were non-diabetic healthy controls. Results: The presence of MTHFR 677T allele did not increase the risk of complications in T2DM patients. The presence of mutant genotypes CT and TT did not increase the risk of nephropathy or other complications in the subjects having a C677T mutation. Conclusion: Methylene Tetrahydrofolate Reductase (MTHFR) C677T gene mutation was neither associated with an increased risk of diabetic nephropathy nor other complications of type II diabetes mellitus.

Hyperbaric oxygen treatment results in a group of Turkish central retinal artery occlusion patients with a combined presence of thrombophilic mutations

Central retinal artery occlusion (CRAO) is a rare ocular-ischemic syndrome causing irreversible blindness. Its pathophysiology has not been clarified, and no targeted therapies are available yet. Hyperbaric oxygen (HBO2) therapy is already an approved therapy for CRAO and has been shown to improve the visual acuity of CRAO patients safely. However, further clinical data are required to classify HBO2 therapy as a type-I general agreement for CRAO. Eleven patients with non-arteritic CRAO were enrolled. Patient demographics, medical history, detailed eye examinations, HBO2 therapy results, pre-/post HBO2 therapy visual acuity measurements and genotypes for common thrombophilic mutations (Factor V G1691A Leiden, Factor II G20210A, MTHFR A1298C, MTHFR C677T, and PAI-1-675 4G/5G) were obtained. Six patients (54%) responded to HBO2 therapy compared to five non-responders (46%). Patients admitted before 12 hours responded well to HBO2 therapy. No systemic diseases nor advanced age were statistically correlated to CRAO. A combination of mutations rather than single mutations for each patient could be seen as responsible for CRAO. No Factor V G1691A Leiden mutations and only one FII G20210A mutation were observed. Eight patients (72%) had MTHFR 677T allele, five patients (45%) had MTHFR 1298C allele, and 10 patients (91%) had the PAI-1-675 4G allele. Not a single mutation but a combination of mutations and other unknown factors probably lead to CRAO, and if intervention is timely, HBO2 therapy offers improvement in visual acuity safely.

The correlation between methylenetetrahydrofolate reductase gene 677C &gt; T polymorphism and fetal congenital defects: A meta-analysis

Abstract Objective To investigate the correlation between the methylenetetrahydrofolate reductase (MTHFR) gene 677C&gt; T polymorphism and fetal congenital defects. Method Original studies relevant to the MTHFR gene 677C&gt;T single nucleotide polymorphism and fetal congenital defects were systematically searched in the electronic databases of Medline, EMBSE and China National Knowledge Infrastructure (CNKI). All relevant publications were screened for inclusion in the present work. The correlation between the MTHFR gene 677C &gt; T single nucleotide polymorphism and the occurrence of fetal congenital defects was expressed as an odds ratio (OR) and its 95% confidence interval (95% CI). Publication bias was assessed by Begg’s funnel plot and Egger’s line regression test. Results Nineteen case-control studies were ultimately included in the present meta-analysis. The pooled results indicated that the general risk of fetal congenital defects was significantly elevated in subjects with the 677T allele of the MTHFR gene in dominant (OR=1.07,95%CI:1.03-1.12, P&lt;0.05), homozygous (OR=1.17,95%CI:1.06-1.30, P&lt;0.05) and recessive genetic models (OR=1.16,95%CI:1.03-1.31, P&lt;0.05) through the random effect method. However, significant publication bias was identified upon pooling the individual data and evaluating the correlation. Conclusion According to the present evidence, the MTHFR gene 677C&gt;T single nucleotide polymorphism is correlated with poor pregnancy outcomes, and subjects with the T allele have an increased risk of developing general fetal congenital defects.

Polymorphisms variants of the MTHFR C677T and PAI-1 5G/4G genes and their combinations in the group of children with arterial ischemic stroke

Introduction. Arterial ischemic stroke (AIS) in childhood is a disorder associated with different predisposing factors, thrombophilia is one of them. We present the study of the MTHFR C677T and PAI-1 5G/4G gene polymorphisms as a possible risk factor for the development of AIS in the group of Ukrainian children. Materials and methods. 77 children from 29 days to 15 years of age were involved in this study: study group - 44 children with AIS, and 33 in a control group. Children enrolled to both groups were at similar age. Results. In the study group there was an increase in the frequency of genotypes 677CT (OR = 2.69) and 677TT, CT + TT genotypes (OR = 3.67) of the MTHFR gene, increased frequency of the 677T allele (OR = 2.57). In the study group detection of 5G/5G + 5G/4G genotypes was higher (OR = 2.82) with statistically predominance of the 5G allele (OR = 2.26) of the gene PAI -1. Higher frequency of the combination of genotypes genes 677CT + 5G/5G was found in the main group. The model of interpreting interactions was built, it allows to predict indirectly the potential intergenic interactions. Conclusions. We conclude that risk of AIS is higher in children with polymorphic variants 677CT and 677TT for the MTHFR gene; the association of polymorphic variants 5G/4G and 5G/5G for the PAI-1 gene with a decrease in the risk of developing AIS; direct interaction with the MTHFR was found for PAI-1, but of weak strength

P322Inhibitors of the renin-angiotensin system in diabetic patients with heart failure with preserved ejection fraction treatment: impact of m235t polymorphism of angiotensinogen

Abstract Background Inhibitors of the renin-angiotensin system plays an important role in chronic heart failure treatment. However, the impact of Angiotensin-converting enzyme (ACE) inhibitors and Angiotensin II receptor blockers (ARBs) on treatment efficacy in diabetic patients with heart failure with preserved preserved ejection fraction (HFpEF) depending on M235T polymorphism of ATG is still unknown. Aim To estimate the efficacy of ACE inhibitors and ARBs therapy in diabetic patient with HFpEF depending on the polymorphism of the M235T of the ATG gene. Methods A total of eighty-two patients (50 females and 32 males; mean age 62,9±8,1 years) with HFpEF and type 2 diabetes mellitus were examined. Sixty-two patients were carriers of 235T allele (MT+TT genotypes), 20 patients had MM genotype of M235T polymorphism of ATG, which was determined by using of polymerase chain reaction. All patients were divided into 4 groups depending on genotypes taking Ramipril or Valsartan during 12 months. Clinical examination, 6 minute walking test, Minnesota Living with Heart Failure Questionnaire (MLHFQ) have been used. All statistical tests were 2-tailed and p&lt;0,05 was considered statistically significant and performed in Statistica 10.0. Results It was not found the significant difference in efficacy of treatment using Valsartan or Ramipril in diabetic patients with genotype MM with HFpEF, whereas in the presence of the T allele of the polymorphism of the M235T ATG, use of valsartan was more effective. Table shows the dynamics of the investigated parameters. Dynamics of parametrs during treatment Parameters HFpEF and DM2T, TT or MT HFpEF and DM2T, MM Ramipril (n=22) Valsartan (n=21) Ramipril (n=10) Valsartan (n=10) Baseline After 12 months treatment Baseline After 12 months treatment Baseline After 12 months treatment Baseline After 12 months treatment SBP, mm Hg 172.0 [157.2; 178.5] 150.0 [132.0; 152.0]* 165.0 [145.3; 174.2] 128.0 [126.0; 134.0]* 167,5 [152.5; 176.0] 140.0 [134.0; 142.0] 160,0 [144.0; 170.0] 146.0 [138.0; 150.0] DBP, mm Hg 98.0 [86.0; 104.0] 92.0 [80.0; 94.0]* 96.0 [82.0; 100.0] 86.0 [80.0; 88.0]* 102.0 [84.0; 106.0] 98.0 [84.0; 100.0] 99.0 [80.0; 100.0] 94.0 [80.0; 96.0] 6 min test, m 313,0 [226,7; 375,5] 320,0 [236,4; 384,6]* 342.5 [258.0; 393.7] 372,0 [262,7; 397,9]* 305.0 [190.5; 375.0] 315.0 [198.5; 384.0] 328.0 [295.0; 401.0] 342.0 [298.0; 410.0] MLHFQ 62,0 [50,0; 71,2] 56,0 [46,5; 68,4]* 61.5 [50.5; 71.5] 40.5 [36.5; 56.5]* 60.0 [47.0; 76.2] 54.0 [43.0; 70.0] 58.0 [49.5; 76.2] 58.0 [49.5; 76.2] Dispnea, % 100 90* 100 70* 100 90 100 80 Edema, % 68,1 54,5* 61,9 33,3* 50 40 60 60 SBP, systolic blood pressure; DBP, diastolic blood pressure; MLHFQ, Minnesota Living with Heart Failure Questionnaire; statistically significant changes (p&lt;0.05). Conclusion Use of Valsartan comparing to Ramipril in diabetic T allele carriers of M235T polymorphism of ATG with HFpEF was independently associated with more effective clinical signs of heart failure improvement, blood pressure decrease, quality of life according to the MLHFQ and physical activity tolerance increase.

Investigating the methylation status of DACT2 gene and its association with MTHFR C677T polymorphism in patients with colorectal cancer.

Colorectal cancer (CRC) is one of the common causes of cancer death in Iranian population. Both genetic and epigenetic changes have been implicated in CRC pathogenesis. DACT2 gene as one of the WNT signaling pathway inhibitor was shown to display tumor suppressor activity in many cancers. The aim of present study was to investigate the methylation status of DACT2 gene and its association with methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in CRC patients. Fifty formalin-fixed paraffin-embedded cancerous and adjacent healthy tissuesobtained from CRC patient were investigated. Genomic DNA was isolated using a FFPE commercial DNA extraction kit. The methylation status was evaluated by methylation specific PCR. Genotyping of MTHFR C677T polymorphism was performed using PCR-RFLP technique. Statistical analysis was done by GraphPad Prism 8. Results indicated that the frequency of methylated DACT2 gene was significantly higher in cancerous tissue relative to adjacent healthy tissue (P<0.001). DACT2 gene methylation was significantly more common among carriers of MTHFR 677CC genotype (P=0.035) and significantly less common among carriers of MTHFR 677T allele (P value =0.006). In conclusion the present study identified DACT2 gene methylation as a significant risk factor for CRC development. Moreover, the low frequency of DACT2 gene methylation among carriers of MTHFR 677T allele may confer a protective role for this common polymorphism against CRC risk.

Contribution of Nitric oxide synthase 3 genetic variants to nasopharyngeal carcinoma risk and progression in a Tunisian population.

We conduct this study to evaluate the clinical and functional impact of Nitric Oxide Synthase 3 (NOS3) T-786C and G894T genetic variants on nasopharyngeal carcinoma (NPC) risk and progression in a Tunisian population. 259 NPC patients and 169 healthy controls were enrolled into our case-control study. Blood samples were genotyped by the RFLP-PCR analysis. The levels of Nitric oxide (NO) were measured by a colorimetric assay kit in the plasma of NPC patients, healthy controls and according to NOS3 genotypes. The correlation between the NOS3 variants and the clinicopathological parameters was examined. We found no linkage disequilibrium between NOS3 T-786C and G894T variants. These results showed that NOS3 variants were genetically independent. In contrast to NOS3 T-786C, a significant association was found between NOS3 G894T polymorphism and NPC risk. The 894T allele decreased significantly in NPC patients and appeared as protective factor (OR = 0.65, CI 95%= 0.48-0.88, p = 0.006). NPC patients had significantly higher levels of plasma NO as compared to healthy controls (p = 0.0011). The T-786C mutation reduced the levels of plasma NO and decreased risk of lymph node metastasis in NPC patients (OR = 0.64, 95% CI = 0.43-0.96; p = 0.03). In contrast, NOS3 G894T polymorphism had no effects neither on NO plasma levels nor clinical parameters. This is the first study to associate NPC with significantly higher levels of plasma NO. NOS3-derived NO could play key roles in NPC pathogenesis. NOS3 variants differently contribute to NPC risk and progression in a Tunisian population. NOS3 G894T was associated with NPC risk. NOS3 T-786C decreased the levels of plasma NO and reduced the development of regional lymph node metastasis.

Methylenetetrahydrofolate Reductase Gene Polymorphism C677T is Associated with Increased Risk of Coronary Heart Disease in Chinese Type 2 Diabetic Patients

Objective Chronic cardiovascular diseases induced by long-term poor blood glucose control are the main cause of death in patients with type 2 diabetes mellitus (T2DM). Previous researches report that methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms might influence the occurrence of coronary heart disease (CHD) in T2DM patients. The purpose of this study was to evaluate whether MTHFR C677T and A1298C mutations are associated with the risk of CHD in T2DM patients. Methods A total of 197 subjects with T2DM were studied, of which 95 patients with CHD. The genotypes of MTHFR C677T and A1298C were analyzed by using dideoxy chain-termination method, and compared between patients with CHD and those without CHD. Results We found that the frequency of the 677T allele was significantly higher in T2DM patients with CHD than those without CHD (P=0.011). However, there was no significant difference in any of the examined haplotypes between T2DM patients with and without CHD. Furthermore, the 677T allele was associated with a higher risk of CHD development in diabetic patients with lower homocysteine (Hcy) levels (≤15 μmol/L) (P=0.006), while no effect of MTHFR gene polymorphism on the incidence of CHD was found in patients with higher Hcy levels (>15 μmol/L) (P=0.491). Conclusion The MTHFR C677T gene polymorphism is associated with the risk of CHD of diabetic patients and could be used as an effective marker for CHD in Chinese diabetic populations with normal Hcy levels.