MTHFR A1298C Research Articles

Development of a high-throughput fluorescence assay for detecting SNPs in hemostasis and folate metabolism genes for clinical use

Genetic predisposition of an individual patient should be taken in account to choose the proper treatment. Implementation to clinical practice requires the development of rapid, high-throughput, and easy assays intended to detect single nucleotide polymorphisms. A detection kit intended to identify the hemostasis and folate cycle gene mutations G20210A FII, G1691A FV, G10976A FVII, G103T FXIII, C807T ITGA2, T1565C ITGB3, 5G(-675)4G PAI, G(-455)A FGB, C677T and A1298C MTHFR, A2756G MTR, A66G MTRR was suggested in this work. The method is based on the polymerase chain reaction and subsequent melt curve analysis of the complexes of amplicons with specific probe. Three single nucleotide polymorphisms can be identified in one tube using our detection kit that increases the productivity of the analysis in the clinical use. Different types of biological samples (buccal epithelium, saliva, plasma, serum, and urogenital swabs) can be used as the initial material for DNA isolation and further analysis by the method developed in this work.

C677T and A1298C gene polymorphisms and sporadic early-onset Alzheimer’s disease

Alzheimer’s disease (AD) is a genetically complex and heterogeneous disorder. Although the clinical manifestations and the pathological features have been well elucidated, a clear etiology of AD is still unknown to this day. In the past few decades, investigations have elucidated that both the genetic and the environmental factors are capable of causing the development of AD. We report a patient with clinically diagnosed earlyonset Alzheimer's disease, age of onset 45 years. Genetic analysis revealed two MTHFR heterozygous polymorphisms C677T and A1298C.

Association between Genetic Polymorphisms of 5,10-Methylenetetrahydrofolate Reductase and Cytokinesis-Block Micronucleus in Peripheral Blood Lymphocyte among 1,3-Butadiene Workers

Exploring the associations between genetic polymorphisms and susceptibility of chromosomal damage induced by 1,3-butadiene(BD) is of much importance for understanding BD carcinogenesis. In current study, we investigated the effects of MTHFR polymorphisms and MTHFR gene haplotype pairs on chromosome damage detected by the cytokinesis-block micronucleus (CBMN) assay in peripheral blood lymphocytes. The data showed that the frequencies of CBMN among BD-exposed workers were significantly associated with the MTHFR A1298C polymorphism (P=0.04 and P=0.03, respectively) by multivariate analysis of covariance. The foundings also showed that the haplotype pairs in the MTHFR gene were more likely than single SNPs to correlate with the BD-induced chromosome damage among occupational exposed workers. Gene-environment interactions between occupational BD exposure and polymorphisms of MTHFR were also evident. These results indicate that the MTHFR polymorphisms may play a role in sensitivity or genetic susceptibility in genotoxic effects of BD exposure in the occupational exposure population.

Asociación entre la alteración del metabolismo de la homocisteína metionina y folato, y el retardo de crecimiento intrauterino idiopático (RCIU). Datos preliminares

Objetivo: el objetivo general de esta investigación es hacer una aproximación para evaluar la asociación entre alteración del metabolismo de la homocisteínametionina y folato en embarazos complicados con restricción de crecimiento intrauterino (RCIU) idiopático, a través del estudio de los niveles de homocisteína pre y posparto, vitamina B12 y folato, así como las frecuencias alélicas y genotípicas de los polimorfismos genéticos de enzimas que participan en la vía metabólica de la homocisteína-metionina y folato en gestantes con embarazos complicados con RCIU idiopático y en condiciones fisiológicas en embarazo normal.Materiales y métodos: estudio piloto observacional analítico de tipo casos y controles. Se estudiaron 8 gestantes con embarazos con restricción de crecimiento intrauterino idiopático y 21 gestantes control con embarazos sin complicaciones y recién nacido sano. Se analizaron las concentraciones de folato, vitamina B12 y homocisteína en el tercer trimestre de embarazo, así como los niveles de homocisteína posparto. Se determinaron los genotipos de las gestantes para los polimorfismos MTHFR C677T, MTHFR A1298C, MTRR A66G, CBS 844ins68, CBS VNTR31pb, CBS C699T y CBS C1080T por medio de reacción en cadena de la polimerasa (PCR) y polimorfismos de longitud de los fragmentos de restricción (RFLP).Resultados: los polimorfismos MTHFR C677T y el genotipo 18/18 del polimorfismo CBS VNTR- 31pb, de manera independiente y en coexistencia, se asociaron a niveles bajos de folato. Igualmente, el genotipo 18/18 del polimorfismo CBS VNTR- 31pb, solo y cuando coexistía con el polimorfismo MTHFR C677T, se asoció con RCIU idiopático.Conclusiones: el metabolismo de la homocisteínametionina y folato es importante para el crecimiento y desarrollo del embrión-feto. El compromiso de estas rutas metabólicas se asocia a complicaciones del embarazo como RCIU idiopático. Los resultados preliminares de este estudio deben incentivar el estudio del metabolismo de la homocisteínametionina y folato en complicaciones del embarazo como la RCIU, así como en condiciones fisiológicas en el embarazo normal en nuestra población.

Determination of the frequency of MTHFR C677T and MTHFR A1298C polymorphisms in persons with polymorphic MTHFR gene

Amac: MTHFR enzimi 5,10 metilentetrahidrofolati 5 metiltetrahidrofolata katalize ederek, homosisteinden metionin remetilasyonu icin gerekli olan aktif folat formunu olusturur. Bu enzimi kodlayan gendeki mutasyonlar ile bir cok hastalik arasindaki iliski arastirilmaktadir. Calismalar, en iyi bilinen MTHFR C677T ve A1298C polimorfizmleri uzerinde yogunlasmaktadir. Bu calisma, MTHFR geninde C677T ve A1298C polimorfizm tespit edilen bireylerde bu polimorfizmlerin sikligini saptamak amaciyla planlanmistir. Gerec ve yontem: Calismaya, Ankara Numune Egitim ve Arastirma Hastanesi III Biyokimya Laboratuvari\'nda C677T ve A1298C yonunden MTHFR polimorfizmi saptanan toplam 164 birey dahil edildi. Hastalarin 44\'u erkek, 120\'si kadindi. Tum hastalarin yas ortalamasi 48,4±16,8 yil (yas araligi 18-76) idi. MTHFR polimorfizmi, ROCHE Light Cycler 1.5 Real Time PCR ile calisildi. Bulgular: Calismaya alinan 164 polimorfizmli bireyin 109\'unda (% 66,5) MTHFR C677T polimorfizmi saptandi. Bu bireylerin 89\'u (% 54,3) heterozigot iken 20\'si (%12,2) homozigot mutant tipti. Yine 95 (%57,9) bireyde A1298C polimorfizmi tespit edildi. Bunlarin 76\'si (%46,3) heterozigot, 19\'u (% 11,6) homozigot mutant genotipe sahipti. Her iki polimorfizmin heterozigot birlikte bulundugu hasta sayisi 40 (% 24,4) idi. Calisma grubunda, MTHFR C677T ve MTHFR A1298C polimorfizm sikliklari acisindan fark tespit edilmedi (p>0,05). Sonuc: Calismamizda, polimorfizm tespit edilen bireylerde, MTHFR A1298C polimorfizminin de C677T kadar sik bulunabilecegi goruldu.

Abstract B01: Meta-analyses of MTHFR and UGT1A1 genes as risk factors for colorectal cancer prevention

Abstract Purpose: The purpose of this meta-analysis was to identify genes that have been associated with colorectal cancer (CRC), and the risk factors associated with these genes for cancer prevention. CRC is the third leading cause of cancer related deaths worldwide. Epidemiological studies have shown that 70-90% of all cancers are related to the environmental behavioral factors and may have implications for cancer prevention. Two genes identified through the genome application framework, and well published in the literature, are methylenetetra-hydrofolate reductase (NAD(P)H) (MTHFR) and UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1). Previous meta-analyses on this topic published 2-3 years ago were based on less than or about 1,000 cases, more focused on identifying the CRC genes. Since then, at least 30 times more cases with controls have been published in the literature, further identifying the potential risk factors for the application of cancer genome and CRC prevention. Procedure: On-line literature were searched from PubMed (PM), PM Central, PM Health databases for systematic reviews and meta-analyses by using a variety of combinations of key words about CRC genes, cancer prevention, human models, and clinical trials. For this analysis, 51 studies that have been published within the last 10 years, published with data containing both control and CRC cases of human samples were identified. These papers were then evaluated with the criteria for the quality of studies. With exclusion of repeated data, 50 studies were included, 46 and 4 studies focused on MTHFR and UGT1A1 respectively. Summary of Data Findings: Preliminary analyses included 31,674 CRC cases and 30,543 controls associating the MTHFR with CRC in 46 studies; and 938 cases and 866 controls associating UGT1A1 gene with CRC in 4 studies. Risk factors identifying the potential benefits of folate and vitamin B's and C are included in the 35 studies that have associated MTHFR with CRC. These studies included samples of all races and many ethnicity groups, and both genders. They have been published across various continents worldwide. While there are inconsistent findings for the association of these genes with CRC, two major single nucleotide polymorphisms (SNPs) for the MTHFR associated with CRC are MTHFR C677T (rs 1801133) and MTHFR A1298C (rs 1801131). The SNP variants in MTHFR have been associated with the prognosis and treatment efficacies of CRC. For prevention, enzyme pathways for folate and vitamin B's or C intake and metabolic mechanisms have been associated with the prognosis and treatment effects of CRC. While folate and associated vitamins have benefits, alcohol intake increases the risks of CRC. Additionally, while a fiber rich diet including cruciferous vegetables and polyphenols from fruits may be beneficial for CRC prevention, smoking may increase the risk and worsen the prognosis. Conclusion: Following analysis of these studies, it can be recommended that primary prevention of CRC could include having a diet rich in fiber, high in folate and vitamin B's and C content, and avoid smoking and heavy alcohol use. Meta-analysis of these studies has important impact for health habits and screening. The most common risks for CRC are preventable with life style changes, such as taking nutritional diet and creating healthy behaviors to help the human epigenetic in-vivo environment free from cancers. Citation Format: Amanda Lie, S. Pamela Shiao, Melissa J. LaBonte, Ching-Yi Chiu, Linda H. Chiang, Rose Sakamoto. Meta-analyses of MTHFR and UGT1A1 genes as risk factors for colorectal cancer prevention. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B01.

Relationships among MTHFR a1298c Gene Polymorphisms and Methylation Status of Dact1 Gene in Transitional Cell Carcinomas

The purpose of this study was to determine the relationship between methylation status of the Dact1 gene and MTHFR a1298c polymorphic forms in transitional cell carcinoma tissues in a Chinese population. Polymorphisms of folate metabolism enzyme gene MTHFR were assessed by restrictive fragment length polymorphism (RFLP) methods and PCR-based DNA methylation analysis was used to determine the CpG island methylation status of the Dact1 gene. Associations between the methylation status of the Dact1 gene and clinical characteristics, as well as MTHFR a1298c polymorphisms, were analyzed. aberrant methylation of the Dact1 gene was found in 68.3% of cancer tissues and 12.4% of normal tissues,. The methylation rate of the Dact1 gene in cancer tissues was significantly higher in patients with lymph node metastasis than in those without lymph node metastasis (46.3% vs. 17.2%, P = 0.018). No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smoking, alcohol consumption and green tea consumption. After adjusting for potential confounding variables, variant allele of MTHFR a1298c was found to be associated with methylation of the Dact1 gene. Compared with wild type CC, the odds ratio was 4.33 (95% CI: 1.06-10.59) for AC and 4.95 (95% CI: 1.18-12.74) for AA. The N stage in TNM staging and the occurrence of lymph node metastasis were associated with an MTHFR 1298 AAμAC genotype (P<0.05). MTHFR 1298 AC and AA genotypes might help maintain a normal methylation status of the Dact1 gene, aberrant CpG island methylation of which is closely related to the genesis and progression of transitional cell carcinoma.

Prevalence of MTHFR, Factor V, ACE and APOE gene polymorphisms among Muslims of Manipur, India

Background: Chronic metabolic disorders such as cardiovascular disease and diabetes have become an emerging public health problem in India, in both rural and urban settings. Genetic markers like MTHFR, FV, ACE and APOE are important candidates involved in the development of these disorders.Aim: The present study aims to understand the distribution of allele frequencies of the SNPs in the above-mentioned genes in Manipuri Muslims, an endogamous religious community constituting∼8% of the Manipur population.Sample and methods: Blood samples were collected from 107 unrelated healthy individuals. Genotyping were done by PCR (for ACE I/D and MTHFR A1298C) followed by restriction digestion (for MTHFR C677T, FV G1691A and APOE).Results and discussion: All four SNPs, with the exception of FVL, were found to be polymorphic, with allele frequencies of 15.1%, 17%, 36.1% and 7.7% for MTHFR 677T, MTHFR 1298C, ACE D and APOE E4, respectively. The D allele of ACE I/D polymorphism was found to be significantly higher among males and also among the young age group compared with females and the old age groups, respectively. This study has highlighted the necessity of looking at the clinical implications of these SNPs in future studies of Manipuri Muslims.

Complex interaction between serum folate levels and genetic polymorphisms in folate pathway genes: biomarkers of prostate cancer aggressiveness

Little is known about the role of folate and polymorphisms associated with folate metabolism on prostate cancer risk in populations of African origin. We examined the relationship between serum folate and prostate cancer and whether any association was modified by genetic polymorphisms for folate metabolism. The study was case-control in design and consisted of 218 men 40-80years old with newly diagnosed, histologically confirmed prostate cancer and 236 cancer-free men attending the same urology clinics in Jamaica, March 2005-July 2007. Serum folate was measured by an immunoassay method and genomic DNA evaluated for MTHR (C677T and A1298C), MTRR A66G, and MTR A2756G polymorphisms. Mean serum folate concentration was higher among cases (12.3±4.1nmol/L) than controls (9.7±4.2nmol/L). Serum folate concentration showed a positive association with prostate cancer (OR, 4.41; CI, 2.52-7.72 per 10nmol/L) regardless of grade. No interactions were observed between genotype and folate concentration, but a weak gene effect was observed for MTHFR A1298C and low-grade prostate cancer. Larger studies to investigate the role of gene-gene/gene-diet interactions in Black men are needed.

Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Acute Lymphoblastic Leukemia-Evidence from an updated meta-analysis including 35 studies

Background5,10-methylenetetrahydrofolate reductase (MTHFR) variants, C677T and A1298C, have been reported to be associated with decreased risk of acute lymphoblastic leukemia (ALL). However, results derived from individually underpowered studies are conflicting. We carried out an updated meta-analysis on the association between MTHFR polymorphisms and ALL risk.MethodsRelevant publications were searched through PUBMED and EMBASE databases. The associations between MTHFR C677T and A1298C polymorphisms and the risk of ALL were evaluated by odds ratios (ORs). The heterogeneity and publication bias were estimated. Meta-regression analysis was performed to evaluate the potential sources of heterogeneity.ResultsC677T polymorphism was associated with a reduced risk of ALL (allele contrast: ORRE = 0.91, 95% CI: 0.83-0.99). Subgroup analysis showed MTHFR C677T variant was associated with decreased susceptibility to ALL in children and Caucasians. Meta-regression showed the logOR for the association between T allele and ALL increased as sex ratio (M/F) in the case group increased (P = 0.01). Regarding A1298C polymorphism, no significant association was observed (allele contrast: ORRE = 1.01, 95% CI: 0.91-1.11). There was no publication bias for C677T or A1298C polymorphism.ConclusionsThe present meta-analysis suggests that the C677T polymorphism, not A1298C, in MTHFR gene is associated with a decreased risk of ALL, particularly among children and Caucasians subjects. Our findings suggest that the influence of the C677T polymorphism on ALL susceptibility is modified by sex ratio in cases (M/F). Since folate intake may be a possible confounding factor, including this factor in future prospective studies is warranted. Further meta-analysis studies should be at least stratified for folate levels and gender to give more powerful and informative results.

Plasminogen Activator Inhibitor 1 and Methylenetetrahydrofolate Reductase Gene mutations in Iranian Women with Polycystic Ovary Syndrome

Mutations in genes related to thrombophilia and hypofibrinolysis have been associated with recurrent pregnancy loss (RPL) and polycystic ovary syndrome (PCOS). Using PCR-RFLP, we investigated the frequencies of MTHFR (A1298C and C677T) as well as PAI-1 (-675 4G/5G) gene polymorphisms in 177 RPL and 100 control women. RPL women were stratified into 38 women with PCOS (RPL-PCOS), 33 with ovarian PCO (RPL-ovarian PCO), and 106 without PCOS (RPL). RPL, RPL-PCOS, and RPL-ovarian PCO groups showed significantly higher frequencies of MTHFR A1298C (P < 0.001) and PAI-1 4G/5G (P < 0.001) mutations than the controls. No significant differences were found between the RPL groups. The respective odds ratios (OR) for bearing MTHFR (A1298C, C677T) and PAI-1 (4G/5G) gene mutations were 33.9-, 2.2-, and 5.2-fold higher in RPL, 66.3-, 6.7-, and 2.8-fold higher in RPL-PCOS, and 27.3-, 1.9-, and 3.9-fold higher in RPL-ovarian PCO women than those in controls. Our results showed the significance of MTHFR A1298C and PAI-1 4G/5G mutations in Iranian women suffering from RPL with and without PCOS.

Polymorphisms in folate‐metabolizing genes and risk of having an offspring with congenital anomalies in the West Siberian region of Russia: a case–control study

Periconceptional folate supplementation prevents a number of congenital anomalies (CA). The aim of our study was to investigate the association of 11 polymorphisms in the folate-metabolizing genes with the risk of having an offspring with CA in the Russian ethnic group. We genotyped 280 mothers having a CA-affected pregnancy and 390 control mothers. The most common malformations among the cases were CA of the nervous, urinary, and cardiovascular systems, and these groups were analyzed separately. In the whole group of CA, we revealed the associations of MTHFR C677T and MTR A2756G loci with increased risk of CA-affected pregnancy. In the group of CA of the cardiovascular system, we observed an association of MTHFR A1298C with decreased risk and an association of MTR A2756G with increased risk of CA. After the Bonferroni correction, only the association between the genotype MTR 2756GG and the risk of having a fetus with CA of the cardiovascular system remained statistically significant (OR = 4.99, P = 0.03). These findings indicate that locus A2756G in the MTR gene may play a role in susceptibility to CA of the cardiovascular system in West Siberia, but further research is necessary to confirm the association.

MTHFR C677T and A1298C polymorphisms and cervical carcinoma susceptibility: meta-analyses based on 4421 individuals

MTHFR polymorphisms have been implicated as risk factors for several cancers. Studies have conducted on the associations of MTHFR polymorphisms with cervical carcinoma risk and have generated inconclusive results. The aim of the present study was to increase power demonstrating the possible relations. Meta-analyses examining the association between MTHFR C677T and A1298C polymorphisms and cervical carcinoma risk were performed. Separate analyses on ethnicity and source of controls were also implemented. Eligible studies were identified for the period up to Dec 2011. Eleven case-control studies containing 1859 cases and 2562 controls regarding MTHFR C677T polymorphisms were selected, of which four studies containing 461 cases and 832 controls described A1298C polymorphisms. For the overall data, no associations of MTHFR C677T polymorphisms with cervical carcinoma were observed (TT vs CC: OR = 1.07; 95 %CI = 0.73-1.58; dominant model: OR = 0.89; 95 %CI = 0.66-1.18; recessive model: OR = 1.13; 95 %CI = 0.84-1.52). In the subgroup analysis by ethnicity, MTHFR 677T allele was associated with decreased cervical cancer susceptibility among Caucasians (TT vs CC: OR = 0.65; 95 %CI = 0.45-0.93; dominant model: OR = 0.70; 95 %CI = 0.58-0.86) but not Asians. As for A1298C polymorphism, no marked associations of A1298C genetic variation with cervical cancer risk were observed (CC vs AA: OR = 1.01; 95 %CI = 0.60-1.73; dominant model: OR = 1.17; 95 %CI = 0.91-1.49; recessive model: OR = 0.99; 95 %CI = 0.60-1.63). Collectively, the results of the present study suggest that MTHFR 677T allele might play a preventive role for cervical carcinoma among Caucasians. A1298C polymorphisms might exert little effect on cervical cancerigenesis.

Folate, MTHFR C677T and A1298C polymorphisms with the relationship with ovarian cancer risk among Chinese females

Genetic and environmental factors may play roles in the pathogenesis of ovarian cancer; we aimed to evaluate the associations between MTHFR C677T and A1298C polymorphism and folate intake with ovarian cancer. A case-control study with 200 ovarian cancer patients and 200 controls were selected in Chinese population from January, 2003 and January, 2006. Genotyping of the MTHFR 677 C4T and 1298 A4C SNPs was performed on the ABI PRISMs 7500 real-time (RT) polymerase chain reaction (PCR) system. Individuals with the TT genotype of C667T polymorphism had an increased risk of developing ovarian cancer (Adjusted OR = 1.76, 95% CI = 1.03 to 3.38) and an increased risk also found in 1298 CC genotype with OR (95% CI) of 2.14 (1.15 to 5.76). Individuals with daily folate consumption > 335 µg/day had a lower risk of ovarian cancer, with an adjusted OR (95% CI) of 0.50 (0.25 to 0.97). The 1298CC genotype was related to a poor survival of ovarian cancer (HR = 2.11, 95% CI = 1.13-4.61). We observed that high folate intake may have a protective role in the development and prognosis of ovarian cancer, and MTHFR gene polymorphisms may be associated with ovarian cancer risk and its prognosis. Key words: Methylenetetrahydrofolate reductase gene, ovarian cancer, folate intake.

Lack of Significance of the BRCA2 Promoter Methylation Status in Different Genotypes of the MTHFR a1298c Polymorphism in Ovarian Cancer Cases in Iran

Promoter methylation, which can be regulated by MTHFR activity, is associated with silencing of genes. In this study we evaluated the methylation status (type) of the BRCA2 promoter in ovarian cancer patients carrying different genotypes of the MTHFR gene (A or C polymorphisms at position 1298). The methylation type of the BRCA2 promoter was evaluated using bisulfate-modified DNA in methylation- specific PCR and the MTHFRa1278c polymorphism was assessed by PCR-RFLP. Analysis of the BRCA2 promoter methylation type of cases showed that 7 out of 60 cases (11.7%) were methylated while the remaining 53 (88.3%) were unmethylated. In methylated cases, one out of the 7 cases had a CC genotype and the remaining 6 methylated cases had an AC genotype. The AA genotype was absent. In unmethylated cases, 34, 18, and one out of these had AC, AA and CC genotype, respectively. There was no significant relationship between the methylation types of the BRCA2 promoter in different genotypes of MTHFRa1298c polymorphism in ovarian cancer; p=0.255. There was no significant relation between the methylation types of the BRCA2 promoter in different genotypes of the MTHFRa1298c polymorphism in ovarian cancer.

Association between MTHFR C677T and A1298C, and MTRR A66G polymorphisms and susceptibility to schizophrenia in a Syrian study cohort

The folate–homocystiene metabolic pathway has been shown to be involved in the susceptibility for developing schizophrenia by several studies. In the present study we investigated the role of three common polymorphisms of the folate–homocysteine metabolic pathway in an Arab population from Syria consisting of 85 schizophrenic patients and 126 healthy controls. The studied polymorphisms included the MTHFR C677T and A1298C, and MTRR A66G, all of which result into amino acid changes, and were previously shown to yield decreased enzymatic activity and alter plasma homocysteine concentration. While MTHFR C677T and A1298C polymorphisms were not previously studied in an Arab population with respect to the susceptibility for developing schizophrenia, the MTRR A66G was not previously investigated in any population around the world. Our results indicated a strong association between MTHFR A1298C and schizophrenia. The variant C allele frequency was significantly higher in the patients group (40% vs 29.4%, OR=1.6, 95% CI (1.06–2.41), p=0.023). A statistically significant association was found for MTHFR 677TT genotype under the recessive model in the male patients subgroup (OR=2.6, 95% CI (1.04–6.5), p=0.036), and MTHFR 677CT genotype under the overdominant model in the total patients group (OR=0.52 95% CI (0.29–0.92), p=0.024). No statistically significant association was found for MTRR A66G polymorphism on an individual basis. However, a borderline association was found for the CC/GG (C677T/A66G) compound genotype (OR=2.24, 95% CI (0.97–5.15), p=0.053). Our results support the hypothesis of association between schizophrenia and folate–homocystiene metabolic pathway genes.

Polymorphisms of MTHFR C677T and A1298C Association With Oral Carcinoma Risk: A Meta-Analysis

Investigations regarding association of MTHFR polymorphisms with oral carcinoma risk have yielded inconclusive results. Thus, meta-analyses were performed. Results showed that no associations of C677T polymorphisms with oral carcinoma were observed for the overall data. In subgroup analyses by drinking status, homozygous TT alleles exhibited elevated oral cancer susceptibility in heavy drinkers. For A1298C polymorphism, CC alleles presented a possible preventive role for oral cancer. Collectively, results suggest that MTHFR 677TT polymorphism might be a low-penetrant risk factor for oral carcinoma only in heavy drinkers. Conversely, 1298CC alleles might play a preventive role for oral cancer.

MTHFR polymorphism and the risk of prostate cancer: a meta-analysis of case–control studies

5,10-Methylenetetrahydrofolate reductase (MTHFR) polymorphisms implicated in the cancer development, but the published studies had yielded inconsistent results. Pubmed was searched for all published case-control studies about MTHFR polymorphisms and prostate cancer risk. In all, 13 studies including 5872 cases and 6255 controls described C677T genotypes, among which 9 articles, containing 2847 cases and 3657 controls described A1298C genotypes, were involved in our meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between MTHFR polymorphisms and prostate cancer risk, heterogeneity, publication bias and sensitivity were also calculated. Overall, meta-analysis indicated that the 677T allele was more likely to exert protective effect on prostate cancer risk (random-effects pooled OR, 0.78 (0.64-0.96); P=0.016 (P=0.033 for heterogeneity studies)) in a recessive genetic model, no associations were found in other genetic models or in comparing a/a versus A/A homozygous. Neither did we find any difference in effects on high or low aggressive prostate cancer. No evidence of an association of MTHFR A1298C polymorphism with prostate cancer was found. C677T of the MTHFR gene may provide protective effects on susceptibility to prostate cancer risk.

Letter to the editor: a meta-analyses of association between polymorphism of MTHFR A1298C and colorectal cancer risk

Letter to the editor: a meta-analyses of association between polymorphism of MTHFR A1298C and colorectal cancer risk

C677T and A1298C polymorphisms of MTHFR gene and their relation to homocysteine levels in Turner syndrome.

To determine the frequency of C677T and A1298C polymorphisms of the MTHFR gene and correlate them with homocysteine serum levels in patients with Turner syndrome (TS) and controls. This case-control study included 78 women with TS and a control group of 372 healthy individuals without personal or family history of cardiovascular disease and cancer. C677T (rs1801133) and A1298C (rs1801131) polymorphisms were detected by polymerase chain reaction-restriction fragment-length polymorphism and the TaqMan system, respectively. Homocysteine serum levels were determined by high-performance liquid chromatography. The results were analyzed statistically, and p<0.05 was considered to represent a significant difference. The homocysteine levels change was 13.9+3.3 nM in patients with TS and 8.8+3.2 nM in the control group. No significant difference between groups was found (p=0.348). Single-marker analysis revealed no association between MTHFR C677T polymorphism and TS when genotype (p=0.063) or allelic (p=0.277) distribution was considered. Regarding MTHFR A1298C polymorphism, a statistical difference was found between the TS group and the control group, for both genotype (p<0.0001) and allele (p<0.0001) distribution. Haplotype analysis of 2 MTHFR polymorphisms identified 2 haplotypes-CC and TC-associated with TS (p<0.001 and p=0.0165, respectively). However, homocysteine levels were not higher in patients with haplotype risk. The results suggest that the C677T and A1298C polymorphisms of the MTHFR gene are not related to homocysteine levels in Brazilian patients with TS, despite the differential distribution of the mutated allele C (A1298C) in these patients. Further studies are needed to investigate the possible genetic interaction with homocysteine levels in TS.