Genetic Polymorphisms of Methylenetetrahydrofolate Reductase Genes and Diffuse Large B-Cell Lymphoma Risk in Middle Eastern Population.

Abstract Diffuse large B-Cell Lymphoma (DLBCL) is one of the most common non-Hodgkin lymphoma types and increased incidence has also been reported during the past 30 years. Methylenetetrahydrofolate (MTHFR) balances the pool of folate coenzymes in one carbon metabolism of DNA synthesis and methylation, both are implicated in carcinogenesis of many types of cancer including lymphoma. Two common variants in the MTHFR gene (C677T and A1298C) have been associated with reduced enzyme activity, thereby making MTHFR polymorphisms a potential candidate caner predisposing factor. These genetic differences are highly race specific and have never been screened in the Saudi DLBCL patients. We conducted hospital-based case control study in the Saudi DLBCL patients. To evaluate the MTHFR C677T and A1298C functional polymorphisms in the MTHFR gene and their association with Saudi DLBCL risk. A hospital based case control study was conducted on a Saudi population- which is known for their genetic homogeneity and high consanguinity- consisting of 187 histologically confirmed DLBCL cases and 513 Saudi controls without a history of cancer. A PCR-RFLP method was used for MTHFR polymorphism genotyping. Data showed that Saudi individuals carrying MTHFR 1298 CC genotype (p<0.001) and genotypes carrying MTHFR 1298C allele (p= 0.012) had 4.23 and 1.73-fold higher risk of developing DLBCL, respectively. Additionally, combined genotype CCCC (MTHFR 677CC+ MTHFR 1298CC) among intermediate MTHFR activity group was associated with 3.489 fold and CTCC (MTHFR 677 CT + 1298CC) among low MTHFR activity group was related to 9.515 fold higher risk, compared with full MTHFR enzyme activity. Our findings suggest that polymorphisms of MTHFR enzyme genes support for the important role of folate metabolism in lymphomagenesis and may be associated with the individual susceptibility to develop DLBCL in Saudi Arabian population. Table 1 Distribution of MTHFR polymorphisms in healthy population and lymphoma patients. Polymorphism Genotype Control group Lymphoma patients p -Methylenetetrahydrofolate reductase (MTHFR) MTHFR C677T CC 372 (72.8%) 109 (68.1%) CT 126 (24.7%) 45 (28.1%) 0.346 1.219 TT 13 (2.5%) 6 (3.8%) 0.404 1.575 CT+TT 139 (27.2%) 51 (31.9%) 0.269 1.252 MTHFR A1298C AA 239 (46.8%) 38 (33.6%) AC 220 (43.1%) 40 (35.4%) 0.625 1.144 CC 52 (10.2%) 35 (31%) <0.001 4.233 AC+CC 272 (53.2%) 75 (66.4%) 0.012 1.734 Table 2 Distribution of combined C677T and A1298C MTHFR genotypes in case and control group. Genotype Control Case p OR ND=Not detected Full Activity group CCAA 157 (30.8%) 22 (27.8%) Intermediate Activity group CCAC 169 (33.2%) 28 (35.4%) 0.649 1.182 CCCC 45 (8.8%) 22 (27.8%) <0.001 3.489 CTAA 69 (13.6%) 13 (16.5%) 0.439 1.345 TOTAL 283 63 0.104 1.589 Low Activity Group CTAC 50 (9.8%) 5 (6.3%) 0.634 0.714 CTCC 6 (1.2%) 8 (10.1%) <0.001 9.515 TTAA 12 (2.4%) 1 (1.3%) 1 0.595 TTAC 0 2 (2.5%) 0.017 ND TTCC 1 (0.2%) - - - TOTAL 69 16 0.189 1.655 Intermediate + Low 352 (69.1%) 79 0.073 1.602

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Methylenetetrahydrofolate Reductase (MTHFR) C677T and A1298C Polymorphisms in Georgian Females with Hypothyroidism

Global Medical Genetics ◽

10.1055/s-0040-1714091 ◽

2020 ◽

Vol 07 (02) ◽

pp. 047-050

Author(s):

Tamar Kvaratskhelia ◽

Elene Abzianidze ◽

Ketevan Asatiani ◽

Merab Kvintradze ◽

Sandro Surmava ◽

...

Keyword(s):

Methylenetetrahydrofolate Reductase ◽

Fragment Length Polymorphism ◽

Mthfr C677t ◽

Mthfr Gene ◽

Control Group ◽

Healthy Individuals ◽

Chain Reaction ◽

Mthfr Polymorphisms ◽

Polymerase Chain ◽

Hypothyroid Patients

AbstractThe aim of this study was to investigate the frequency of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in Georgian females with hypothyroidism. Thirty-four patients and 29 healthy individuals were recruited in this study. Polymerase chain reaction-restriction fragment length polymorphism analyses were used for genotyping of MTHFR polymorphisms. The results of this study suggest that the MTHFR C677T variant was significantly associated with hypothyroidism. In addition, in individuals with T allele risk of hypothyroidism significantly increased. Combination of CT/AA genotypes was more prevalent in the hypothyroid patients than in the control group. Thus, C677T polymorphism could be a possible genetic factor contributing to the pathophysiology of hypothyroidism, possibly through hyperhomocysteinemia.

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Methylenetetrahydrofolate reductase polymorphisms as risk factors for retinal venous occlusive disease: A literature review

European Journal of Ophthalmology ◽

10.1177/11206721211000647 ◽

2021 ◽

pp. 112067212110006

Author(s):

Manuel Marques ◽

Francisco Alves ◽

Miguel Leitão ◽

Catarina Rodrigues ◽

Joana Tavares Ferreira

Keyword(s):

Risk Factors ◽

Literature Review ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

Mthfr Gene ◽

Mthfr Polymorphisms ◽

Vein Occlusion ◽

C677t Mutation ◽

Retinal Vascular Disease

The role of polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene in retinal vein occlusion (RVO) is a theme of discussion since the first reports of RVO in patients with MTHFR C677T mutation and without classic acquired risk factors for retinal vascular disease. The association between MTHFR polymorphisms and RVO has been studied over the last 20 years producing conflicting results. This review aims to summarize the literature concerning the role MTHFR polymorphisms as risk factors for RVO.

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Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in breast cancer: a Sardinian preliminary case-control study

International Journal of Medical Sciences ◽

10.7150/ijms.32162 ◽

2019 ◽

Vol 16 (8) ◽

pp. 1089-1095 ◽

Cited By ~ 3

Author(s):

Paolo Castiglia ◽

Valeria Sanna ◽

Antonio Azara ◽

Maria R. De Miglio ◽

Luciano Murgia ◽

...

Keyword(s):

Breast Cancer ◽

Methylenetetrahydrofolate Reductase ◽

Case Control Study ◽

Mthfr C677t ◽

Case Control ◽

Control Study

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Clinicopathologic characteristics and outcomes of transformed diffuse large B-cell lymphoma in hepatitis C virus-infected patients: A case-control study of 84 patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.7553 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 7553-7553

Author(s):

Jeff Hosry ◽

Roberto N. Miranda ◽

Francesco Turturro ◽

Minas P. Economides ◽

Felipe Samaniego ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Case Control Study ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Cell Phenotype ◽

First Line ◽

Clinicopathologic Characteristics ◽

Large B Cell Lymphoma ◽

Control Study

7553 Background: Chronic hepatitis C virus (HCV) infection is associated with development of marginal zone lymphoma (MZL) and diffuse large B-cell lymphoma (DLBCL). Preliminary data showed particular characteristics of HCV-associated DLBCL; such as frequent transformation from indolent lymphomas and aggressive oncologic courses. We studied herein the clinicopathologic characteristics and outcomes of HCV-infected patients (pts) with transformed DLBCL. Methods: In this case control study, the medical records and pathology reports of HCV-infected (cases) and HCV-uninfected (controls) pts with transformed DLBCL seen at our institution (6/2004 - 5/2015) were reviewed. Included pts had a concomitant or a history of a low grade lymphoma. To determine their clinicopathologic characteristics, cases were compared to controls at a ratio of 1:3. To determine predictors of oncologic relapse, we compared pts with DLBCL relapse after first line chemotherapy to those who did not relapse in univariate and logistic regression analyses. Results: Twenty-one cases were compared to 63 controls. Compared to controls, cases were younger (median year age [interquartile range], 54 [49-62] v 62 [53-66], P = .01), had advanced Ann Arbor stages, 3-4 (95% v 76%, P = .05), and upper gastro-intestinal involvement (48% v 25%, P = .05). Immunophenotypically, cases had more CD10-negative B-cells (76% v 43%, P = .008) and CD5-positive B-cells (39% v 7%, P = .004) compared to controls, consistent with an activated B-cell phenotype. A comparison between pts who relapsed after first line chemotherapy (n = 42) and those who did not (n = 40) revealed that having CD5-positive B-cells was the only factor associated with DLBCL relapse in univariate (24% v 6%, P = .03) and multivariate analyses (OR = 10.7, P= .02). Conclusions: HCV-infected pts with transformed DLBCL are younger, present with advanced stages, are more commonly CD5-positive, and have an activated B-cell phenotype, suggesting more frequent transformation from MZL compared to HCV-uninfected pts. The higher frequency of CD5-positive B-cells might explain the higher DLBCL relapses previously described in HCV-infected pts.

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Evaluation of c677t and a1298c polymorphism of the methylenetetrahydrofolate reductase gene as a maternal risk factor for trisomy 21 (a monocentric study)

Revista Romana de Medicina de Laborator ◽

10.1515/rrlm-2017-0003 ◽

2017 ◽

Vol 25 (1) ◽

pp. 27-35

Author(s):

Simona Bucerzan ◽

Radu Anghel Popp ◽

Raluca Maria Vlad ◽

Cecilia Lazea ◽

Radu Nicolaescu ◽

...

Keyword(s):

Trisomy 21 ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr Gene ◽

Control Group ◽

Healthy Children ◽

Mthfr Polymorphisms ◽

Maternal Risk ◽

Reductase Gene ◽

A1298c Polymorphism ◽

Methylenetetrahydrofolate Reductase Gene

Abstract Aim: To assess the risk for trisomy 21 in children, depending on the polymorphisms C677T and A1298C of the methylenetetrahydrofolate reductase (MTHFR) gene in mothers. Methods: For 93 mothers who have children with trisomy 21 and 202 mothers of healthy children (control group), genotyping of MTHFR polymorphisms C677T and A1298C was performed. Results: For each polymorphism, three genotypes were identified (normal homozygous, heterozygous and mutant homozygous). For the polymorphism C677T, the frequencies of the three genotypes (CC, CT and TT) were 50.5%, 40.8% and 8.6% in mothers of children with trisomy 21, versus 42.6%, 46% and 11.4% in mothers of healthy children, with no statistically significant differences. The frequency of the polymorphism A1298C was not statistically significant between the two groups for the genotype (AA) (48.4% vs 56.4%) or the genotype (AC) (39.8% vs 38.6%), but the genotype TT was more frequent in mothers of children with trisomy 21 (11.8% vs 4.9%; p = 0.033; OR = 2.57). Conclusion: Women with genotype CC for the polymorphism A1298C of the MTHFR gene have a 2.57 times higher risk of offspring with trisomy 21.

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A case-control study investigating the effect of MTHFR C677T variant on performance of elite athletes

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1568026620666201022144819 ◽

2020 ◽

Vol 20 ◽

Author(s):

Ayse Feyda Nursal ◽

Serbulent Yigit ◽

Husniye Rustemoglu ◽

Abdullah Cenikli

Keyword(s):

Athletic Performance ◽

Methylenetetrahydrofolate Reductase ◽

Elite Athletes ◽

Mthfr C677t ◽

Mthfr Gene ◽

Control Group ◽

Genotype Distribution ◽

Significant Difference ◽

Pcr Rflp ◽

Strength Of Association

Objective: Increased level of plasma homocysteine (Hcy) is a potential risk factor for several multi-system diseases. The Methylenetetrahydrofolate reductase (MTHFR) gene C677T variant has been established as an important genetic determinant of hyperhomocysteinemia. There are conflicting reports about the effects of physical activity on plasma Hcy. Therefore, the main aim of this study was to investigate whether the MTHFR C677T variant affects the elite athletic performance. Methods: This study was carried out on 214 individuals (114 elite athletes and 100 sedentary controls). Genotyping was performed using PCR- RFLP method. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Results: There was a significant difference between the athletes and the control group in genotype distribution and allele frequency of the MTHFR C677T variant. MTHFR C677T CC genotype and C allele were more prevalent in elite athletes than those in the sedentary controls (p =0.007, OR: 2.16, 95%:1.26-3.70; p=0.009, OR: 1.84, 95%:1.18-2.89, respectively). The control group had a higher MTHFR C677T CT genotype than the athletes had (p=0.019, OR: 0.51, 95%:0.30-0.88). There was no deviation from HWE for the MTHFR C677T variant in the groups. Conclusion: Our findings support that there is an association between the MTHFR C677T C allele and athletic performance among the elite Turkish athletes.

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Oxidative Stress and Polymorphism in MTHFR SNPs (677 and 1298) in Paternal Sperm DNA is Associated with an Increased Risk of Retinoblastoma in Their Children: A Case–Control Study

Journal of Pediatric Genetics ◽

10.1055/s-0038-1667037 ◽

2018 ◽

Vol 07 (03) ◽

pp. 103-113 ◽

Cited By ~ 2

Author(s):

Shilpa Bisht ◽

Bhavna Chawla ◽

Rima Dada

Keyword(s):

Oxidative Stress ◽

Case Control Study ◽

Case Control ◽

Mthfr Gene ◽

Nucleotide Polymorphisms ◽

Mthfr Polymorphisms ◽

Sperm Dna ◽

Increased Risk ◽

Control Study

AbstractSperm DNA is considered as the most vulnerable to oxidative stress-induced damage that also impairs global sperm DNA methylation leading to sperm-associated pathologies. C677T and A1298C polymorphisms of the methylene tetrahydrofolate reductase (MTHFR) gene affect MTHFR enzyme activity. This study was planned as a case–control study to determine the MTHFR gene polymorphisms in the fathers of children affected with sporadic nonfamilial heritable retinoblastoma in an Indian population. MTHFR polymorphisms for single nucleotide polymorphisms 677 and 1298 were also determined in sporadic nonfamilial heritable retinoblastoma patients to estimate the risk for retinoblastoma development and to evaluate the role of MTHFR in retinoblastoma pathogenesis.

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