MTHFR C677T Variant Research Articles

Drug Response of Iranian Alzheimer's Patients to Rivastigmine Concerning Their Genotype for VDR rs11568820 and MTHFR C677T Variants: A Pharmacogenetic and Association Study.

Alzheimer's disease is a neurodegenerative disorder with polygenic etiology. Genetic risk variants for Alzheimer's disease differ among populations. Thus, discovering them in each population is clinically important. A total of 118 patients and 97 controls for VDR rs11568820 and 88 patients and 100 healthy controls for MTHFR C677T polymorphism were genotyped to evaluate the association of these polymorphisms with late-onset Alzheimer's disease in the Iranian population, along with their impacts on the response to Rivastigmine treatment. The VDR C allele was significantly associated with Alzheimer's disease and provided protection against it (P = 0.003, RR = 1.14, 95% CI 1.04-1.24), while the T allele increased susceptibility (P = 0.003, RR = 1.93, 95% CI 1.23-3.02). These results were also considerable upon excluding the effect of APOE ε4 allele. The Prevalence-corrected Positive Predictive Value was 1.71% for the VDR CC genotype and 4% for the VDR CT genotype, indicating lower and almost twofold higher chances of developing Alzheimer's disease, respectively. No significant correlation was observed between MTHFR C677T and Alzheimer's disease. Based on our pharmacogenetic study, MTHFR T allele carriers lacking APOE ε4 allele showed a better response to Rivastigmine treatment after a 2-year follow-up. Moreover, patients with VDR CC genotype displayed milder Alzheimer's disease, particularly when coincided with the APOE ε4 allele. The VDR rs11568820 polymorphism affects both Alzheimer's disease risk and the response to Rivastigmine in Iranian patients. Also, MTHFR C677T polymorphism may play a role in the response to Rivastigmine, through a pathway that needs to be elucidated in future studies.

Factor V Leiden G1691A, Prothrombin G20210A, and MTHFR C677T Mutations among Sudanese Women with Recurrent Pregnancy Loss

Background: Various factors, such as genetic causes, anatomic abnormalities of the uterus, infectious diseases, coagulative disorders, and endocrinological and immunological diseases, might influence recurrent pregnancy loss (RLP). This study aimed to evaluate the prevalence and frequency of the FII G20210A, FVL G1691A, and MTHFR C677T polymorphisms in Sudanese women with RPL. Methods and Results: This descriptive cross-sectional study involved 100 women with a history of 3 or more RPLs (the case group) and 94 healthy multiparous women without pregnancy complications (the control group). DNA was extracted from peripheral blood samples. The study of the FII G20210A, FVL G1691A, and MTHFR C677T polymorphisms was performed by PCR and RFLP analysis. For the FII G20210A, the genotype distribution in the case group and control group was as follows: GG=97.0%, GA=3.0%, AA=0% and GG=94.0%, GA=0%, AA=0%, respectively. In the case group, the allelic distribution was as follows: G=98.5%, A=1.5%. In the control group, the A allele was absent, and the frequency of the G allele was 100%. For the MTHFR C677T, the genotypic and allelic frequencies in the case group were 97%, 3%, and 0%, respectively, for the CC, CT, and TT genotypes, and 98.5% and 1.5%, respectively, for the C and T alleles. In the control group, the genotype distribution was as follows: CC-100% CT-0%, TT-0%; the T allele was absent, and the frequency of the C allele was 100%. For the FVL G1691A, the genotype distribution in the case group and control group was as follows: GG=92.0%, GA=8.0%, AA=0% and GG=93.6%, GA=6.4%, AA=0%, respectively. For G and A alleles, the frequencies were 96.0% and 4.0%, respectively, for the case group, and 96.8% and 3.2%, respectively, for the control group. Our analysis did not reveal a significant positive association between the MTHFR C677T, FII G20210A, and FVL G1691A polymorphisms and the risk of RPL across the dominant model, multiplicative model, and a comparison of the frequencies of the heterozygous and homozygous dominant genotypes. Conclusion: The research findings suggest that the MTHFR C677T, FVL G1691A, and FII G20210A variants do not significantly contribute to the increased susceptibility to RPL in this specific population of Sudanese women. Continued scientific inquiry is crucial for developing more nuanced and personalized strategies for the diagnosis and prevention of RPL, ultimately improving women's reproductive health.

Involvement of the ABCB1 C3435T Variant but Not the MTHFR C677T or MTHFR A1298C Variant in High-Dose Methotrexate-Induced Toxicity in Pediatric Acute Lymphoblastic Leukemia Patients in China.

It remains unclear whether the MTHFR C677T, MTHFR A1298C and ABCB1 C3435T genetic variants are associated with methotrexate (MTX) elimination delay and high-dose MTX (HD-MTX) toxicities in the treatment of pediatric acute lymphoblastic leukemia (ALL). The aim of our study was to analyze the potential predictive role of MTHFR C677T, MTHFR A1298C and ABCB1 C3435T in toxicities and the relationship between these variants and MTX elimination delay during HD-MTX therapy in pediatric ALL patients. We conducted a retrospective study on ALL patients receiving HD-MTX treatment with available MTHFR C677T, MTHFR A1298C and ABCB1 C3435T genotype and 44-h plasma MTX levels. Logistic regression analyses and chi-square tests were used to assess the relationship between the variants and HD-MTX toxicities and MTX elimination delay. Genotype frequencies were in Hardy-Weinberg equilibrium. MTX elimination delay did not significantly differ between MTHFR C677T and MTHFR A1298C or ABCB1 C3435T. Leukopenia (P=0.028), neutropenia (P=0.034) and oral mucositis (P=0.023) were 6.444-fold, 4.978-fold and 9.643-fold increased, respectively, in ABCB1 C3435T homozygous genotype (TT) patients compared to wild-type (CC) patients. No significant association was found between the toxicities investigated and MTHFR C677T or MTHFR A1298C. This study showed that the ABCB1 C3435T homozygous allele genotype (TT) is associated with increased MTX-related toxicities (leukopenia, neutropenia and oral mucositis). These results may help to distinguish pediatric ALL patients with a relatively high risk of MTX-related toxicities before HD-MTX infusion and optimize MTX treatment.

Associations between one-carbon metabolism and valproic acid-induced liver dysfunction in epileptic patients.

Valproic acid (VPA) has been widely used as an antiepileptic drug for decades. Although VPA is effective and well-tolerated, long-term VPA treatment is usually associated with hepatotoxicity. However, the underlying mechanisms of VPA-caused hepatotoxicity remain unclear. In this study, a total of 157 pediatric patients with epilepsy were recruited and divided into normal liver function (NLF, 112 subjects) group and abnormal liver function (ABLF, 45 subjects) group. We observed that MTHFR A1298C and MTHFR C677T variants may be linked to VPA-induced liver dysfunction (p = 0.001; p = 0.023, respectively). We also found that the MTHFR A1298C polymorphism was associated with a higher serum Hcy level (p = 0.001) and a lower FA level (p = 0.001). Moreover, the serum Hcy levels was strongly correlated with the GSH and TBARS concentrations (r = -0.6065, P < 0.001; r = 0.6564, P < 0.001, respectively). Furthermore, logistic analysis indicated that MTHFR A1298C/C677T polymorphisms and increased Hcy concentrations may be risk factors for VPA-induced liver dysfunction. These results suggested that individual susceptibility to VPA-induced liver dysfunction may result from MTHFR A1298C/C677T polymorphisms and increased Hcy levels. This study may be helpful for the prevention and guidance of VPA-induced liver dysfunction.

Association between MTHFR C677T variant and risk for congenital heart defects in Egyptian children: a case–control study including meta-analysis based on 147 cases and 143 controls

BackgroundStratification analysis studies showed that ethnicity has a significant association regarding MTHFR C677T variant and congenital heart diseases (CHDs) risk, and many published studies have controversial conclusions toward this association.MethodsIn this study, the association between the MTHFR C677T variant and the risk for CHDs was evaluated in 91 children with CHD and 95 healthy controls, as new cases, by using restriction fragment length polymorphism (RFLP) technique. Besides that, 2 case–control studies in the Egyptian population published before 2021 were included in this meta-analysis. The association was assessed by the odds ratio (OR) with a 95% confidence interval (CI) based on 294 alleles in CHD cases and 286 alleles in controls.ResultsThe overall meta-analysis showed a significant association between MTHFR C677T variant and CHDs risk in Egyptian children with heterogeneity (Heterogeneity = 0.001) in all the genetic models with the highly significant association in T versus C allele (pooled OR 1.89, 95% CI 1.31–2.74; p value < 0.0004). The consistency of the genotypes was detected by Hardy–Weinberg equilibrium (HWE).ConclusionsOur results support the MTHFR -677T allele as a susceptibility factor for CHDs in the Egyptian pediatric patients.

ONE-CARBON METABOLISM GENE POLYMORPHISM CORRELATE WITH LEVELS OF DNA METHYLTRANSFERASES IN PATIENTS WITH MIGRAINE

Migraine is a common, disabling disorder characterized by attacks of 4 to 72 h of severe headache and associated autonomic and neurological symptoms.&nbsp;In the present study we analyzed the expression of DNMT1, DNMT3a, and DNMT3b in patients with migraine compared with healthy controls as well as the association between the levels of DNMTs and the LINE-1 methylation status in migraine patients with MTHFR C677T variant. Materials and Method: A total 48 individuals were enrolled in this study (24 patients with migraine and 24 age-matched healthy controls). The study protocol was approved by the Ethics Committee of Tbilisi State Medical University. Results: We observed that methylation of LINE-1 were correlated with the levels of&nbsp;DNMT3a in migraine. In addition, levels of DNMT1, DNMT3a and DNMT3b in patients with TT genotypes of MTHFR gene rs1801133 polymorphism were significantly lower compared with individuals with CC genotypes. Conclusions: Differential levels DNMTs may play an important role in the pathogenesis of migraine. Further investigation of enzymes involved in DNA methylation with larger number of samples may provide important insight into the development of novel treatments for episodic and/or chronic migraine.

The impact of pre-pregnancy folic acid intake on placental DNA methylation in a fortified cohort.

Folate plays an important role in the modulation of one-carbon metabolism and DNA methylation through a complex biosynthesis pathway. Folate deficiency during pregnancy has been associated with an increased risk for birth defects. This study investigates the extent to which the availability of folate and S-Adenosylmethionine (SAM) affects placental DNA methylation. We hypothesized that maintaining sufficient levels of folate and SAM is particularly important in individuals carrying the MTHFR C677T polymorphism. Maternal- and cord blood was analyzed to genotype the MTHFR rs1801133 SNP. Red blood cell (RBC) folate, vitamin B12, SAM, and S-Adenosylhomocysteine (SAH) were analyzed in cord blood. Epigenome-wide methylation analyses were performed on 90 placenta tissue samples isolated from the fetal side of the placenta; 45 originating from mother-infant dyads homozygous for the MTHFR C677T variant and 45 originating from mother-infant dyads with the homozygous wild type MTHFR677 genotype. Verification of the results was performed using pyrosequencing assays. Genome-wide placental DNA methylation patterns were relatively stable and not significantly affected by levels of one-carbon metabolites. MTHFR genotype was associated with DNA methylation of several loci, including a locus in the MTHFR region. RBC folate and particularly the SAM:SAH ratio did affect overall CpG DNA methylation in some CpG regions when the loci were split according to their CpG island relation. This was most evident in participants carrying the MTHFR C677T variant suggesting a stronger influence of the biosynthesis pathway on the overall placental DNA methylation in MTHFR TT individuals than in MTHFR CC individuals.

Serum L-Carnitine Levels Are Associated With First Stroke in Chinese Adults With Hypertension.

This study aimed to evaluate the association of serum L-carnitine with first stroke and explore potential effect modifiers. This is a nested, case-control study drawn from the China Stroke Primary Prevention Trial among rural Chinese adults with hypertension, including 557 first stroke cases and 557 age-matched, sex-matched, treatment group-matched, and residence-matched controls. Serum L-carnitine was measured by liquid chromatography with tandem quadrupole mass spectrometry. Multiple conditional logistic regression models were used to evaluate the association between L-carnitine and first stroke. The mean level of serum L-carnitine in the stroke population was 4.7 μg/mL, which was significantly lower than that of the control group (5.7 μg/mL). When L-carnitine was assessed as quintiles, compared with the reference group (quintile 1, <3.3 μg/mL), the odds of stroke were 0.62 (95% CI, 0.39-1.00) in quintile 2, 0.66 (95% CI, 0.40-1.10) in quintile 3, 0.47 (95% CI, 0.28-0.81) in quintile 4, and 0.50 (95% CI, 0.30-0.84) in quintile 5. The trend test was significant (P=0.01). When quintiles 2 to 5 were combined, the adjusted odds ratio of first stroke was 0.58 (95% CI, 0.38-0.87) compared with quintile 1. Similar associations were found for ischemic stroke and hemorrhagic stroke. In subgroup analysis, a significant L-carnitine-stroke association was only observed in the normal folate group (P interaction, 0.039) and in the MTHFR CC genotype group (P interaction, 0.047). In this study of rural Chinese adults with hypertension, serum L-carnitine had an inverse but nonlinear association with first stroke. Folate status and the MTHFR C677T variant were significant effect modifiers of the association.

Is the MTHFR C677T variant a genetic risk factor in the etiology of autism spectrum disorder? Is it alone or by combined with rare variants of the PHGDH gene? Running Title: Is the MTHFR C677T a genetic risk factor for autism?

Is the MTHFR C677T variant a genetic risk factor in the etiology of autism spectrum disorder? Is it alone or by combined with rare variants of the PHGDH gene? Running Title: Is the MTHFR C677T a genetic risk factor for autism?

MTHFR C677T and A1298C variants in Mexican Mestizo infants with neural tube defects from Western Mexico.

Our study investigated the role of MTHFR C677T and A1298C variants in infants with neural tube defects (NTDs) from western Mexico. Using TaqMan allelic discrimination assay, we genotyped 101 live-born patients with NTDs (cases) and 247 controls. Our findings do not support that homozygosity or heterozygosity for the variants C677T and A1298C in the MTHFR gene are associated with NTDs in infants. However, since we have the highest worldwide frequency of homozygotes for the MTHFR C677T variant, we cannot rule out that our propensity for NTDs may be related to how such gene variant interacts with other factors, mainly with our secular patterns of inappropriate folate intake.

A prospective study to explore the relationship between MTHFR C677T genotype, physiological folate levels, and postpartum psychopathology in at-risk women.

The etiology of postpartum psychopathologies are not well understood, but folate metabolism pathways are of potential interest. Demands for folate increase dramatically during pregnancy, low folate level has been associated with psychiatric disorders, and supplementation may improve symptomatology. The MTHFR C677T variant influences folate metabolism and has been implicated in depression during pregnancy. To conduct a prospective longitudinal study to explore the relationship between MTHFR C677T genotype, folate levels, and postpartum psychopathology in at-risk women. In the first three months postpartum, folate will moderate a relationship between MTHFR genotype and depression, with TT homozygous women having more symptoms than CC homozygous women. We recruited 365 pregnant women with a history of mood or psychotic disorder, and at 3 postpartum timepoints, administered the Edinburgh Postnatal Depression Scale (EPDS); Clinician-Administered Rating Scale for Mania (CARS-M) and the Positive and Negative Symptom Scale (PANSS) and drew blood for genotype/folate level analysis. We used robust linear regression to investigate interactions between genotype and folate level on the highest EPDS and CARS-M scores, and logistic regression to explore interactions with PANSS psychosis scores above/below cut-off. There was no significant interaction effect between MTHFR genotype and folate level on highest EPDS (p = 0.36), but there was a significant interaction between genotype, folate level and log(CARS-M) (p = 0.02); post-hoc analyses revealed differences in the effect of folate level between CC/CT, and TT genotypes, with folate level in CC and CT having an inverse relationship with symptoms of mania, while there was no relationship in participants with TT genotype. There was no significant interaction between MTHFR genotype and folate level on the likelihood of meeting positive symptom criteria for psychosis on the PANSS (p = 0.86). These data suggest that perhaps there is a relationship between MTHFR C677T, folate level and some symptoms of postpartum psychopathology.

Increased homocysteine expression associated with genetic changes in the folate pathway as a key determinant of preeclampsia: A prospective study from lower Assam, India

Lacunae exist in the scientific understanding of preeclampsia (PE) pathogenesis, which is a global issue and a clinical challenge during pregnancy and contributes to both maternal and fetal morbidity and mortality. We aim to understand the significance of homocysteine levels and folate pathway parameters in PE pathogenesis involving pregnancy cases from lower Assam, India. PE cases {N = 145, mild-PE (n = 108), severe-PE (n = 37)} and 192 normal full-term delivery cases were evaluated for Hcy expression and Vitamin B12 levels and evaluated for association with MTHFR and TYMS polymorphisms in PE pathogenesis. Hcy level was significantly higher in PE cases with negative pregnancy outcomes (p = 0.003) and was higher in PE-preterm delivery compared to PE-term delivery cases (p = 0.301). The VitaminB12 levels were not associated with higher tHcy concentration. Distribution of MTHFRC677T variant genotype was significantly higher in severe-PE cases compared to mild-PE cases (p = 0.050) and was associated with an increased risk of severe PE. The combined variant genotype of MTHFR and TYMSdel6 polymorphism resulted in significant increase (p = 0.014) in the risk of severe-PE compared to mild-PE. Within the PE delivery group, the combined variant genotypes showed association with higher homocysteine levels both in live birth cases as well in the PE cases with negative pregnancy outcomes. Increased homocysteine levels were associated with combined variant genotypes and were consistent in both term and preterm delivery in PE cases. The study points out the prognostic significance of MTHFR C677T, TYMS 1494del6 genotype and tHcy levels as a risk factor for PE, negative pregnancy outcome and preterm delivery.

Association of MTHFR C677T polymorphism with elevated homocysteine level and disease development in vitiligo.

Increasing evidence on the association of MTHFR gene polymorphism and serum homocysteine levels with autoimmune diseases such as vitiligo has made the MTHFR gene a very interesting candidate to be evaluated in different ethnicities and populations. We aimed to evaluate the levels of serum homocysteine and vitamin B12 and their associations with MTHFR C677T polymorphism in the Iranian population. This case-control study included 104 patients with vitiligo and 100 age- and sex-matched healthy control subjects. Serum vitamin B12 and homocysteine levels were measured by a chemiluminescence assay. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used for genotyping the polymorphism. The mean serum homocysteine levels were significantly higher in cases than controls and associated with disease activity (p<.001). Furthermore, the homozygous MTHFR C677T variant genotype was associated with vitiligo development (adjusted OR: 3.52, 95% CI: 1.09-11.32, p=.02) and elevated homocysteine level (p<.001). There was no association between serum vitamin B12 levels and the MTHFR C677T genotype. The homozygous variant MTHFR C677T may be considered as a risk factor for both elevated homocysteine levels and the development of vitiligo in the Iranian population. Although these results are not conclusive, they could elucidate the contribution of genetic and immune-mediated inflammatory factors to the pathogenesis of vitiligo.

Polymorphisms of folate metabolism regulators increase risk of meiosis II nondisjunction of chromosome 21 in oocyte

We have tested maternal polymorphic variants MTR A2756G (rs1805087), MTRR A66G (rs1801394), MTHFR C677T (rs1801133) and MTHFR A1298C (rs1801131) for their association with meiotic errors in oocyte and Down syndrome birth among 730 controls and 1019 case mothers having Down syndrome child from Bengali speaking population of India. We demonstrated significant association of MTR A2756G (rs1805087), MTRR A66G (rs1801394), MTHFR A1298C (rs1801131), but not MTHFR C677T (rs1801133) variants with maternal meiosis II nondisjunction in maternal age independent manner. Moreover, the mutant genotypes of two tested loci when co-occurred exhibited synergistic effect and increase the risk of Down syndrome birth many folds. In silico analyses predicted the probable damages of the transcripts or proteins from respective genes owing to said polymorphisms among the women. These findings from the largest sample population tested ever bring us a significant step closer towards understanding the relation between folate metabolism, meiotic error and Down syndrome birth.

Hereditary thrombophilia genetic variants in recurrent pregnancy loss.

The relationship between thrombophilia genes and recurrent pregnancy loss has been discussed. The aim of this study was to investigate the association between of MTHFR C677T, A1298C, F2G20210A, and F5 G1691A genetic variants among Iranian women with recurrent miscarriage. A total of 245 women with two or more recurrent pregnancy loss, with mean age years were enrolled in the study. To compare genotypes, we have selected 250 healthy women without history of miscarriage as control group. Genomic DNA of participants was evaluated using polymerase chain reaction followed by Sanger sequencing to determine the genotype frequency. The mean age were 32.16 ± (21-42) and 31.81 ± (19-40) for case and control groups respectively. MTHFR C677T and A1298C mutant alleles were found to be significantly more prevalent in patients than control. However, F2G20210A and F5 G1691A genetic variants showed no significance. The allele frequencies for the assessed genotypes in this study are consistent with the data obtained for other countries. We observed significant susceptible effects of MTHFR C677T, and A1298C among participants. According to the relatively high prevalence of these variants, we recommend genetic testing for women with RPL before therapeutic decisions.

Interactions between genetic variants involved in the folate metabolic pathway and serum lipid, homocysteine levels on the risk of recurrent spontaneous abortion

BackgroundThe interaction between folate pathway gene polymorphisms and homocysteine, serum lipid leverls are poorly understood in patients with recurrent spontaneous abortion (RSA). The aim of this study is to explore the effects of folate pathway gene polymorphisms (the 5–10-methylenetetrahydrofolate reductase, MTHTR C677T, MTHFR A1298C and the methionine synthase reductase, MTRR A66G) and their interactions with homocysteine on serum lipid levels in patients with RSA.MethodsA total of 403 RSA women and 342 healthy women were randomly selected. Genotyping of the MTHFR C677T, A1298C and MTRR A66G were performed by TaqMan-MGB technique. Serum homocysteine, folate, fasting glucose, fasting insulin, Interleukin 6, Tumor necrosis factorα (TNFα) and lipid profiles were measured according to the kits. Continuous variables were analyzed using 2-sample t-tests. Categorical variables were analyzed and compared by χ2 or Fisher’s exact tests. Unconditional logistic regression model was applied to test the interactions of gene polymorphisms on RSA.ResultsThe distribution of genotype of CC, CT TT and T allele of MTHFR C677T, genotype of AA and C allele of MTHFR A1298C, and genotype of AA, AG and G allele of MTRR A66G were different between cases and controls (all p were < 0.05). There were significant interactions between MTHFR C677T-A1298C and MTHFR A1298C-MTRR A66G in RSA group and control group, with ORs of 1.62 (95%CI: 1.28–2.04, p < 0.001) and 1.55 (95%CI: 1.27–1.88, p < 0.001), respectively. Serum TNFα level and insulin resistant status (HOMR-IR) were higher in RSA group than in control group (p = 0.038, 0.001, respectively). All the three gene SNPs except MTRR 66AG gene variant had detrimental effects on HOMA-IR (all p were < 0.05). RSA group who carried the MTHFR 677CT, TT, CT/TT genotypes and MTRR 66AG, AG/GG genotypes had detrimental effects on serum homocysteine levels, the MTHFR 677CT, CT/TT genotype carriers had favorable effects on serum folate levels, the MTHFR 677TT, CT/TT, 1298 AC, AC/CC genotype carriers had detrimental effects on serum low-density lipoprotein cholesterol (LDL-C) levels, and the MTRR 66AG genotype carriers had lower high-density lipoprotein cholesterol (HDL-C) levels than the AA genotype carriers (all p were < 0.05).ConclusionsInteraction between the MTHFR C677T, A1298C and MTHFR A1298C, MTRR A66G are observed in our RSA group. Besides, all the three gene SNPs except MTRR 66AG gene variant had detrimental effects on HOMA-IR. MTHFR C677T and MTRR A66G gene variants had detrimental effects on serum homocysteine levels and insulin resistance status, while MTHFR C677T, A1298C and MTRR A66G gene variants had detrimental effects on certain serum lipid profiles.

Impact of methylenetetrahydrofolate reductase C677T polymorphism on the efficacy of photodynamic therapy in patients with neovascular age-related macular degeneration

The most severe visual impairments due to age-related macular degeneration (AMD) are frequently caused by the occurrence of choroidal neovascularization (CNV). Although photodynamic therapy with verteporfin (PDT-V) is currently a second-line treatment for neovascular AMD, it can be conveniently combined with drugs acting against vascular endothelial growth factor (anti-VEGF) to reduce the healthcare burden associated with the growing necessity of anti-VEGF intravitreal re-injection. Because the common 677 C > T polymorphism of the methylenetetrahydrofolate reductase gene (MTHFR-C677T; rs1801133) has been described as predictor of satisfactory short-term responsiveness of AMD-related CNV to PDT-V, we retrospectively examined the outcomes of 371 Caucasian patients treated with standardized, pro-re-nata, photodynamic regimen for 24 months. Responder (R) and non-responder (NR) patients were distinguished on the basis of the total number of scheduled PDT-V (TN-PDT-V) and change of best-corrected visual acuity (∆-BCVA). The risk for both TN-PDT-V and ∆-BCVA to pass from R to NR group was strongly correlated with CT and TT genotypes of MTHFR-C677T variant resulting, respectively, in odd ratios of 0.19 [95% CI, 0.12–0.32] and 0.09 [95% CI, 0.04–0.21] (P < 0.001), and odd ratios of 0.24 [95% CI, 0.15–0.39] and 0.03 [95% CI, 0.01–0.11] (P < 0.001). These pharmacogenetic findings indicate a rational basis to optimize the future clinical application of PDT-V during the combined treatments of AMD-related CNV, highlighting the role of thrombophilia to be aware of the efficacy profile of photodynamic therapy.

The association of the MTHFR C677T polymorphism with inflammatory bowel diseases in the Israeli Jewish population: An example of genetic heterogeneity.

MTHFR C677T is a common gene polymorphism that has been shown to be associated with hyperhomocysteinemia. Studies on the role of MTHFR in inflammatory bowel diseases (IBD) have yielded conflicting results, perhaps due in part to genetic heterogeneity. The prevalence of the MTHFR C677T variant allele varies according to Jewish subpopulations: Ashkenazi vs non-Ashkenazi. The aim of this study was to examine the association between MTHFR C677T genotype and IBD in the different Jewish populations.DNA samples were assessed for the presence of the MTHFR C677T variant allele in 445 Jewish Israeli IBD patients: 338 with Crohn's disease [CD] (214 Ashkenazi and 124 non-Ashkenazi Jews) and 107 with ulcerative colitis [UC] (73 Ashkenazi and 34 non-Ashkenazi Jews), and in 347 healthy controls: 173 Ashkenazi and 174 Non-Ashkenazi Jews. Possible genotype–phenotype associations were investigated.We showed a significantly higher frequency of MTHFR 677T variant genotypes in non-Ashkenazi CD patients: Odds ratio of 1.86 for heterozygotes (CT) and 2.89 for homozygotes (TT) compared to non-Ashkenazi healthy controls. No significant association was found for UC in non-Ashkenazi patients or for CD or UC in Ashkenazi patients.Our findings suggest that the MTHFR 677T variant may contribute to the risk of CD in non-Ashkenazi but not Ashkenazi Jews. This may result from genetic heterogeneity and highlights the complexity of the genetic etiology of IBD.

The relationship between MTHFR C677T gene polymorphism and essential hypertension in a sample of an Algerian population of Oran city

BackgroundMany studies have investigated the role of 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism in essential hypertension (EH), but with conflicting results. AimTo determine the eventual association between 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and hypertension in a sample of Algerian population from the Oran city. MethodsA case–control study has been performed in 154 subjects including 82 hypertensives defined as subjects with elevated systolic blood pressure SBD≥140mmHg and or sustained diastolic blood pressure DBP≥90mmHg, and 72 normotensive subjects. Polymerase chain reaction (PCR) combined with restrictive fragment length polymorphism (RFLP) was used to detect the MTHFR C677T variant. ResultsWe observe no significant differences between allelic and genotypic frequencies between cases and controls for C677T polymorphism (OR=1.51, 95% CI=0.89–2.56, P=0.13). Analyses adjusted for age, sex and body mass index improved the association level, though the association was still not significant (30% vs. 22%, OR=1.75, 95% CI=0.95–3.24, P=0.07). ConclusionThis work showed that genetic polymorphism related to the MTHFR gene (C677T) is not associated with the risk of hypertension in this sample of Algerian population. Larger case–control samples are required to clearly assess the role of this genetic variant in EH.

Association between MTHFR C677T polymorphism and diabetic nephropathy in the Chinese population: An updated meta-analysis and review.

To clarify the effects of MTHFR C677T polymorphism on the risk of diabetic nephropathy (DN) in the Chinese population, an updated meta-analysis was performed. Related studies were identified from PubMed, Springer Link, Ovid and Chinese Databases up to 24 February 2015. A total of 15 studies including 1227 DN cases, 586 healthy controls and 1277 diabetes mellitus (DM) controls were involved in this meta-analysis. Overall, a significantly elevated risk of DN was associated with all variants of MTHFR C677T when compared with the healthy group (T vs C, odds ratio (OR) = 2.22, 95% confidence interval (CI) = 1.88-2.61; TT vs CC, OR = 4.22, 95% CI = 3.02-5.90; TT + CT vs CC, OR = 2.62, 95% CI = 2.07-3.31; TT vs CC + CT, OR = 2.81, 95% CI = 2.08-3.81) or DM (T vs C, OR = 1.78, 95% CI = 1.59-2.00; TT vs CC, OR = 2.95, 95% CI = 2.33-3.73; TT + CT vs CC, OR = 1.93, 95% CI = 1.63-2.29; TT vs CC + CT, OR = 2.31, 95% CI = 1.87-2.84). In subgroup analyses stratified by ethnicity and geographic areas, it revealed the significant results in Chinese Han, in North and South China. The risk conferred by MTHFR C677T polymorphism is higher in North China than in South China. This meta-analysis showed that the MTHFR C677T variants may influence DN risk in Chinese, and further studies with gene-gene and gene-environment interactions are required for definite conclusions.