Assessment of the relationship between methylenetetrahydrofolate reductase polymorphism and acute lymphoblastic leukemia: Evidence from an updated meta-analysis

2020 ◽  
Vol 26 (7) ◽  
pp. 1598-1610
Author(s):  
Rim Frikha

Objective The methylenetetrahydrofolate reductase gene C677T polymorphism is closely related to the acute lymphoblastic leukemia. Several case–control studies have investigated this association; however, no conclusions could be drawn. A comprehensive updated meta-analysis is established to explain these contradictions and clarify the overall impact of this variant on the susceptibility to acute lymphoblastic leukemia. Methods Electronic searches were conducted to select published studies prior to June 2018. Pooled odds ratios and stratification analysis were performed under different genetic comparison models, age, and ethnicity. Results Totally, 66 case–control studies including 9619 acute lymphoblastic leukemia cases and 17,396 controls were selected. Our analyses showed that methylenetetrahydrofolate reductase C677T polymorphism was protective mainly in Asian and European countries, under all genetic models and regardless of age, but leukemogenic in mixed population. Conclusion Thus, C677T polymorphism may be a promising acute lymphoblastic leukemia biomarker, but they should be interpreted with caution considering other factors such as folic acid intake, gene–gene and gene–environment interactions.

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Fereshteh Aliakbari ◽  
Farkhondeh Pouresmaeili ◽  
Nahal Eshghifar ◽  
Zahra Zolghadr ◽  
Faezeh Azizi

Abstract Background and objectives One of the possible male sterility risk factors are polymorphisms of Methylenetetrahydrofolate reductase (MTHFR). However, the epidemiologic investigations described inconsistent results regarding MTHFR polymorphism and the risk of male infertility. For that reason, we carried out a meta-analysis of published case-control studies to re-examine the controversy. Methods Electronic searches of Cochrane, EMBASE, Google Scholar, and PubMed were conducted to select eligible studies for this meta-analysis (updated to May 2019). According to our exclusion and inclusion criteria, only high-quality studies that remarked the association between MTHFR polymorphisms and male infertility risk were included. The Crude odds ratio (OR) with a confidence interval of 95% (CI) was used to assess the relationship between MTHFR polymorphism and male infertility risk. Results Thirty-four case-control studies with 9662 cases and 9154 controls concerning 677C/T polymorphism and 22 case-control studies with 5893 cases and 6303 controls concerning 1298A/C polymorphism were recruited. Both MTHFR polymorphisms had significant associations with male infertility risk (CT + TT vs. CC: OR = 1.37, 95% CI: 1.21–1.55, P = 0.00, I2 = 41.9%); (CC vs. CA + AA: OR = 0.82, 95% CI: 0.52–1.30, P = 0.04, I2 = 50.1%). Further, when stratified by ethnicity, the significant association results were observed in Asians and Caucasians for 677C/T and just Asians for 1298A/C. Conclusions Some of MTHFR polymorphisms like MTHFR 677C > T are associated with an elevated male infertility risk. To confirm our conclusion and to provide more accurate and complete gene-environment communication with male infertility risk, more analytical studies are needed.


2020 ◽  
Author(s):  
Jin Liu ◽  
Gu Weiling ◽  
Li Xueqin ◽  
Xie Liang ◽  
Wang Linhong ◽  
...  

Abstract Background: We performed an updated meta-analysis to clarify the relationship between the CEBPE rs2239633 polymorphism and the CALL susceptibility.Methods: All the case-control studies updated on July 31, 2019 through Web of Science, Pubmed, Cochrane Library, Embase, China Nationa Knowledge Infrastructure (CNKI) electronic database. The heterogeneity in the study was tested by the Q-test and I2, and then the random ratio or fixed effect was utilized to merge the odds ratios (OR) and 95% confidence interval (CI). To estimate the impact of individual studies on aggregate estimates, we performed sensitivity analysis. Using funnel plot and Begger’s regression test investigated the publication bias. All data Statistical analyses were performed using Stata 12.0.Results: A total of 23442 participants (7014 patients; 16428 controls) were included in twenty case-control studies selected. There was no association of CEBPE rs2239633 polymorphism with CALL (CC vs CT + TT: OR = 1.08, 95% CI = 0.94 –1.26; CC + CT vs TT: OR = 1.10, 95% CI = 0.94–1.30; C vs T: OR =1.02, 95% CI = 0.92–1.13). In the subgroup analysis by ethnicity, no significant association of this polymorphism and CALL risks among Asia and Caucasian populations for the comparison of CC vs CT + TT, CC + CT vs TT and C vs T genetic models .Conclusion: This meta-analysis did not find the CEBPE rs2239633 polymorphism can increase and decrease the risk of susceptibility to CALL.


2020 ◽  
Vol 40 (2) ◽  
Author(s):  
Sheng Zhang ◽  
Jiakai Jiang ◽  
Weifeng Tang ◽  
Longgen Liu

Abstract C677T (Ala>Val, rs1801133 C>T), a non-synonymous variant of methylenetetrahydrofolate reductase (MTHFR) gene, has been found to be associated with an impair enzyme activity of MTHFR. The relationship of MTHFR rs1801133 with hepatocellular carcinoma (HCC) has been extensively investigated. However, the findings were conflicting. Recently, more investigations have been conducted on the relationship of MTHFR rs1801133 with HCC. To obtain a more precise assessment on the effect of this non-synonymous variant to the development of HCC, a pooled-analysis was performed. This meta-analysis consisted of 19 independent case–control studies. By using the odds ratio (OR) combined with 95% confidence interval (CI), the relationship of MTHFR rs1801133 with HCC risk was determined. A total of 19 independent case–control studies were included. Finally, 6,102 HCC cases and 6,526 controls were recruited to examine the relationship of MTHFR rs1801133 with HCC risk. In recessive model (TT vs. CC/CT), the findings reached statistical significance (OR, 0.90; 95%CI, 0.82–0.98; P = 0.016). Subgroup analysis also found an association between MTHFR rs1801133 polymorphism and the decreased risk of HCC in hepatitis/virus related patients (recessive model: OR, 0.85; 95%CI, 0.72–0.99; P = 0.035, and allele model: OR, 0.90; 95%CI, 0.81–0.99; P = 0.028). Subgroup analyses indicated that extreme heterogeneity existed in Asian population, larger sample size investigation, hospital-based study and normal/healthy control subgroups. The shape of Begger’s seemed symmetrical. Egger’s linear regression test also confirmed these evaluations. Sensitivity analyses suggested that our findings were stable. In summary, our results highlight that MTHFR rs1801133 polymorphism decreases HCC susceptibility. The relationship warrants a further assessment.


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