Association of MTHFR C677T and A1298C Polymorphisms with Susceptibility to Chronic Lymphocytic Leukemia: A Systematic Review and Meta-Analysis

Background: The relation between methylenetetrahydrofolate reductase)MTHFR( polymorphisms and the risk of developing Chronic lymphocytic leukemia (CLL) is not still clear, while there are reports about the association of MTHFR C677T and A1298C polymorphisms with developing CLL, there are other reports that rolled out the association of MTHFR polymorphisms with developing CLL. Therefore herein we carried out this meta-analysis to clear the association of MTHFR polymorphisms with the risk of CLL Methods: A comprehensive search was performed through PubMed, Scopus and Embase from inception to Aug 2020. Odds ratios (OR) with their corresponding 95% confidence intervals (CI) for five possible genetic models were calculated. Heterogeneity was evaluated using the Cochran Q test and the I2 statistic. Results: Totals of 1290 cases and 1887 controls for the C677T polymorphism and 1117 cases and 1256 controls for the A1298C polymorphism were included in our analysis. Analyzing the MTHFR C677T and A1298C polymorphisms genotypes showed an association between MTHFR polymorphism at A1298C under Allelic model and the risk of CLL (OR = 1.12, 95% CI = 1.01–1.25), however there was no association between MTHFR polymorphism at MTHFR C677T and risk of CLL. Conclusion: The risk of developing CLL might be associated with MTHFR polymorphism at A1298C under allelic model and not associated with MTHFR polymorphisms at C677T, However, further studies considering other factors such as age, gender, ethnicity, gene-gene interaction and environmental condition are needed to clear the true association of MTHFR polymorphisms with CLL.

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Association Between MTHFR Polymorphisms and the Risk of Essential Hypertension: An Updated Meta-analysis

Frontiers in Genetics ◽

10.3389/fgene.2021.698590 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hao Meng ◽

Shaoyan Huang ◽

Yali Yang ◽

Xiaofeng He ◽

Liping Fei ◽

...

Keyword(s):

Sensitivity Analysis ◽

Essential Hypertension ◽

Methylenetetrahydrofolate Reductase ◽

Meta Analysis ◽

Mthfr C677t ◽

Cochrane Library ◽

Mthfr Polymorphisms ◽

Southeast Asians ◽

Increased Risk ◽

Meta Analyses

Background: Since the 1990s, there have been a lot of research on single-nucleotide polymorphism (SNP) and different diseases, including many studies on 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism and essential hypertension (EH). Nevertheless, their conclusions were controversial. So far, six previous meta-analyses discussed the internal relationship between the MTHFR polymorphism and EH, respectively. However, they did not evaluate the credibility of the positive associations. To build on previous meta-analyses, we updated the literature by including previously included papers as well as nine new articles, improved the inclusion criteria by also considering the quality of the papers, and applied new statistical techniques to assess the observed associations. Objectives: This study aims to explore the degree of risk correlation between two MTHFR polymorphisms and EH. Methods: PubMed, EMBASE, the Cochrane Library, CNKI, and Wan Fang electronic databases were searched to identify relevant studies. We evaluated the relation between the MTHFR C677T (rs1801133) and A1298C (rs1801131) polymorphisms and EH by calculating the odds ratios (OR) as well as 95% confidence intervals (CI). Here we used subgroup analysis, sensitivity analysis, cumulative meta-analysis, assessment of publication bias, meta-regression meta, False-positive report probability (FPRP), Bayesian false discovery probability (BFDP), and Venice criterion. Results: Overall, harboring the variant of MTHFR C677T was associated with an increased risk of EH in the overall populations, East Asians, Southeast Asians, South Asians, Caucasians/Europeans, and Africans. After the sensitivity analysis, positive results were found only in the overall population (TT vs. CC: OR = 1.14, 95% CI: 1.00–1.30, Ph = 0.032, I2 = 39.8%; TT + TC vs. CC: OR = 1.15, 95% CI: 1.01–1.29, Ph = 0.040, I2 = 38.1%; T vs. C: OR = 1.14, 95% CI: 1.04–1.25, Ph = 0.005, I2 = 50.2%) and Asian population (TC vs. CC: OR = 1.14, 95% CI: 1.01–1.28, Ph = 0.265, I2 = 16.8%; TT + TC vs. CC: OR = 1.17, 95% CI: 1.04–1.30, Ph = 0.105, I2 = 32.9%; T vs. C: OR = 1.10, 95% CI: 1.02–1.19, Ph = 0.018, I2 = 48.6%). However, after further statistical assessment by FPRP, BFDP, and Venice criteria, the positive associations reported here could be deemed to be false-positives and present only weak evidence for a causal relationship. In addition, when we performed pooled analysis and sensitivity analysis on MTHFR A1298C; all the results were negative. Conclusion: The positive relationships between MTHFR C677T and A1298C polymorphisms with the susceptibility to present with hypertension were not robust enough to withstand statistical interrogation by FPRP, BFDP, and Venice criteria. Therefore, these SNPs are probably not important in EH etiology.

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Methylenetetrahydrofolate Reductase Polymorphisms and Pregnancy Outcome

Geburtshilfe und Frauenheilkunde ◽

10.1055/a-0664-8237 ◽

2018 ◽

Vol 78 (09) ◽

pp. 871-878 ◽

Cited By ~ 9

Author(s):

Mert Turgal ◽

Fatma Gumruk ◽

Ergun Karaagaoglu ◽

Mehmet Beksac

Keyword(s):

Pregnancy Outcome ◽

Pregnancy Outcomes ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

Study Groups ◽

Mthfr Polymorphism ◽

Mthfr C677t Polymorphism ◽

Mthfr Polymorphisms ◽

Group I ◽

Significant Difference

Abstract Introduction Aim of the study was to evaluate the effect of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on pregnancy outcome. Materials and Methods A total of 617 pregnancies of women who were investigated for MTHFR C677T and A1298C polymorphisms prior to pregnancy were included in the study. Cases were classified into “homozygous polymorphisms” (Group I), “heterozygous polymorphisms” (Group II), and patients without polymorphisms who functioned as controls (Group III). Patients with polymorphisms were assigned to a specific protocol at least 3 months before becoming pregnant. Administration of low molecular weight heparin (LMWH) was started very early during pregnancy. The Beksac Obstetrics Index (BOI) was used to estimate the obstetric risk levels for the different groups. Results We found that the early pregnancy loss (EPL) rate increased as MTHFR polymorphism complexity increased and that the early EPL rate was significantly higher in patients with MTHFR C677T polymorphism compared to patients with MTHFR A1298C polymorphism (p = 0.039). There were significant differences between the previous pregnancies of the patients in the 3 study groups in terms of perinatal complications and EPLs (p = 0.003 and p = 0.019). The BOI decreased as the severity of polymorphisms increased. An association between MTHFR polymorphisms and congenital malformations and chromosomal abnormalities was observed. We could not demonstrate any statistically significant difference between study groups when the 3 groups were compared with regard to the pregnancy outcomes under specific management protocols. Conclusion MTHFR polymorphisms are potential risk factors for adverse pregnancy outcomes.

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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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Impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on methotrexate-induced toxicities in acute lymphoblastic leukemia: a meta-analysis

Tumor Biology ◽

10.1007/s13277-012-0395-2 ◽

2012 ◽

Vol 33 (5) ◽

pp. 1445-1454 ◽

Cited By ~ 47

Author(s):

Lin Yang ◽

Xin Hu ◽

Luhang Xu

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Methylenetetrahydrofolate Reductase ◽

Lymphoblastic Leukemia ◽

Meta Analysis ◽

Mthfr Polymorphisms

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Reduced Intensity Conditioning Yields Superior Overall Survival Rates Compared to Myeloablative Regimens for Allogeneic HCT in Chronic Lymphocytic Leukemia: A Side-By-Side Systematic Review/Meta-Analysis

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2016.12.170 ◽

2017 ◽

Vol 23 (3) ◽

pp. S269 ◽

Cited By ~ 1

Author(s):

Jessica El-Asmar ◽

Tea Reljic ◽

Ambuj Kumar ◽

Mohamed A. Kharfan-Dabaja

Keyword(s):

Systematic Review ◽

Overall Survival ◽

Chronic Lymphocytic Leukemia ◽

Meta Analysis ◽

Survival Rates ◽

Lymphocytic Leukemia ◽

Reduced Intensity Conditioning ◽

Allogeneic Hct ◽

Reduced Intensity ◽

Overall Survival Rates

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Non-Association of Methylenetetrahydrofolate Reductase (MTHFR) Polymorphisms with Homocysteine Levels, Venous or Arterial Thromboses in 1,141 North-Central Appalachian Patients

Cancer and Clinical Oncology ◽

10.5539/cco.v5n2p21 ◽

2016 ◽

Vol 5 (2) ◽

pp. 21

Author(s):

Farhad Khimani ◽

Peter Perrotta ◽

Gerry Hobbs ◽

Thomas Hogan

Keyword(s):

Risk Assessment ◽

Patient Population ◽

Methylenetetrahydrofolate Reductase ◽

Plasma Homocysteine ◽

Minimal Cost ◽

Frequency Pattern ◽

Mthfr Polymorphism ◽

Mthfr Polymorphisms ◽

North Central ◽

Central Appalachia

Objectives: MTHFR polymorphism testing has been used by clinicians for thrombophilia risk assessment. We questioned the utility of such testing.Methods: 1,141 patients age 18 and above had MTHFR testing for both C677T and A1298C polymorphisms, 2006 through 2012. Available plasma homocysteine levels were obtained and ICD-9 billing codes were grouped to identify venous or arterial clots in these patients.Results: 901 women and 240 men were tested; median age in women was 33 years (range 18-86); median age in men was 47 years (range 18-83). County of residence mapping confirmed that this MTHFR tested population was from north-central Appalachia. Only 144 (13%) of the 1,141 patients had no polymorphism at either the C677T or the A1298C locus; only 4 patients (0.4%) had 3 or more polymorphisms; 993 patients (87%) had either one or two polymorphisms. We found polymorphism frequency pattern similar in both sexes. Although men had higher homocysteine levels, MTHFR polymorphisms did not associate with homocysteine levels in either sex. In 901 women tested, the ICD-9 coded incidence of arterial clots was 20%, and of venous clots was 21%; in 240 men tested, the incidence of arterial clots was 48% and of venous clots was 40%. MTHFR polymorphisms did not associate with arterial or venous clots in either sex. Based on CPT billing codes, a minimal cost estimate was $137,000 for performing these 1,141 MTHFR tests.Conclusions: MTHFR testing was costly and did not add useful information during thrombophilia evaluation in this patient population.

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