scholarly journals Methylenetetrahydrofolate reductase C677T (Ala>Val, rs1801133 C>T) polymorphism decreases the susceptibility of hepatocellular carcinoma: a meta-analysis involving 12,628 subjects

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.

2020 ◽  
Vol 20 (1) ◽  
pp. 351-358
Author(s):  
Yingwei Wang ◽  
Peiyang Hu

Background: Inconsistent results have been reported from studies investigating the relationship of the interleukin-10 (IL-10) -1082 G/A polymorphism and the susceptibility of hepatocellular carcinoma (HCC). Therefore, a thorough literature review of relatedstudies was performed in this meta-analysis to examine the association of the interleukin-10(IL-10) -1082 G/A poly- morphism with HCC susceptibility. Methods: Electronic databases were searched for literature on the relationship between interleukin-10(IL-10) -1082 G/A poly- morphism and the risk of HCC in accordance with the inclusion and exclusion criteria. The selected studies were analyzed using the Stata 12.0 software. Finally, the strength of the associations was evaluated using the odds ratio (OR) and 95% confidence intervals (95% CI). Results: A total of six case-control studies were enrolled into the current meta-analysis, which included a total of 911 patients and 1889 control subjects. Our data revealed no association between the IL-10 -1082 G/A polymorphism and the risk of HCC (GG vs AA:OR=0.84, 95%CI=0.57-1.25; AG vs AA:OR=0.85, 95%CI=0.70-1.05; Dominant model: OR=0.85, 95%CI=0.70- 1.03; and Recessive model: OR=0.92, 95%CI = 0.64-1.32). Similarly, no association was found in sub-group analysis based on ethnicity. Conclusion: The results of our study suggest no association between IL-10 -1082 G/A polymorphism and the risk of HCC. Keywords: Hepatocellular carcinoma; IL-10 polymorphism; risk analysis. 


2019 ◽  
Vol 74 (3) ◽  
pp. 251-256 ◽  
Author(s):  
Hailong Su ◽  
Guo Zhang

Background: The correlation between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and hepatocellular carcinoma (HCC) remains controversial. Objectives: We performed this study to better assess the relationship between MTHFR gene polymorphisms and the likelihood of HCC. Methods: A systematic research of PubMed, Medline, and Embase was performed to retrieve relevant articles. ORs and 95% CIs were calculated. Results: A total of 15 studies with 8,378 participants were analyzed. In overall analyses, a significant association with the likelihood of HCC was detected for the rs1801131 polymorphism with fixed-effect models (FEMs) in recessive comparison (p = 0.002, OR 0.62, 95% CI 0.43–0.82). However, no positive results were detected for the rs1801133 polymorphism in any comparison. Further subgroup analyses revealed that the rs1801131 polymorphism was significantly associated with the likelihood of HCC in Asians with both FEMs (recessive model: p < 0.0001, OR 0.42, 95% CI 0.29–0.62; allele model: p = 0.004, OR 1.20, 95% CI 1.06–1.35) and random-effect models (recessive model: p = 0.002, OR 0.47, 95% CI 0.29–0.75). Nevertheless, we failed to detect any significant correlation between the rs1801133 polymorphism and HCC. Conclusions: Our findings indicated that the rs1801131 polymorphism may serve as a genetic biomarker of HCC in Asians.


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.


2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Jiakai Jiang ◽  
Sheng Zhang ◽  
Weifeng Tang ◽  
Zhiyuan Qiu

Abstract Previous studies suggested that miR-146a rs2910164 (C/G) locus was predicted to influence the risk of cancer. However, the relationship of miR-146a rs2910164 locus with colorectal cancer (CRC) susceptibility was controversial. We recruited 1003 CRC patients and 1303 controls, and performed a case–control study to clarify the correlation of miR-146a rs2910164 locus with CRC risk. Subsequently, a comprehensive meta-analysis was conducted to verify our findings. In the case–control study, we suggested that miR-146a rs2910164 variants did not alter CRC risk (CG vs. CC: adjusted P=0.465; GG vs. CC: adjusted P=0.436, CG/GG vs. CC: adjusted P=0.387 and GG vs. CC/CG: adjusted P=0.589), even in subgroup analysis. Next, we conducted a pooled-analysis to identify the correlation of miR-146a rs2910164 locus with CRC risk. In this pooled-analysis, 7947 CRC cases and 12,168 controls were included. We found that miR-146a rs2910164 polymorphism did not influence the risk of CRC (G vs. C: P=0.537; GG vs. CC: P=0.517, CG/GG vs. CC: P=0.520 and GG vs. CC/CG: P=0.167). Our findings suggest that miR-146a rs2910164 C/G polymorphism is not correlated with the susceptibility of CRC. In the future, more case–control studies are needed to confirm our results.


2020 ◽  
Author(s):  
Jin Shu ◽  
Jun Ling Li ◽  
Yujuan Fu ◽  
Xuelian Hui ◽  
Yani Jin ◽  
...  

Abstract Background Postmenopausal osteoporosis (PMO) is the most common type of primary osteoporosis. ESR1 polymorphism rs2234693 and rs9340799 has been widely studied as a candidate gene associated with PMO, however, the findings were inconclusive. The present study aims to explore the relationship of ESR1 polymorphism rs2234693 and rs9340799 with PMO risk in a Chinese Han population. Methods A total of 230 unrelated PMO patients and 150 control were recruited. DNA of all participants was extracted from the peripheral blood samples and genotyped by Mass Array method. A meta-analysis of case control studies was also conducted to further elucidate the relationship of polymorphism with PMO. Results Our results revealed that there were no associations of the rs2234693 with PMO. However,GG genotype of rs9340799 was associated with a higher risk of PMO (OR=1.51, 95%CI:1.08-4.34, p=0.03), even adjusting for risk factors (OR=1.83, 95%CI: 1.12-5.04, p=0.04). Logistic regression analysis showed the dominant model was associated with a higher risk of PMO (OR = 2.07, 95%CI: 1.02-5.16, p=0.02) after correcting the risk factors (OR=2.14, 95%CI:1.12-5.64, p=0.04); In addition, the Meta-analysis results revealed that both two polymorphisms were not associated with PMO. Conclusion In conclusion,ESR1 polymorphism rs9340799 was associated with PMO, However, well designed study with larger sample sizes, is required to further elucidate these association.


2021 ◽  
Vol 104 (2) ◽  
pp. 003685042110136
Author(s):  
Huaguo Wang ◽  
Yi Wang

No consistent results have been reached on the relationship of interleukin-1 (IL-1) rs1800587 polymorphism with the susceptibility to rheumatoid arthritis (RA) so far. Therefore, the current meta-analysis was designed to thoroughly review relevant studies, in order to examine the relationship of IL-1A rs1800587 polymorphism with RA risk. Electronic databases were retrieved for literature regarding the relationship between IL-1A rs1800587 polymorphism and RA vulnerability according to the inclusion and exclusion criteria. Stata 12.0 software was adopted to examine the enrolled literature. Meanwhile, odds ratio (OR) and corresponding 95% confidence intervals (95% CI) were used to evaluate the association. A total of seven case-control researches (3267 patients and 2960 healthy controls) were eventually enrolled into the current meta-analysis. Our data indicated no correlation of IL-1A rs1800587 polymorphism with RA risk (TT vs CC: OR = 0.90, 95% CI = 0.73–1.11; TC vs CC: OR = 1.02, 95% CI = 0.78–1.34; Dominant model: OR = 1.04, 95% CI = 0.80–1.35; Recessive model: OR = 1.91, 95% CI = 0.74–1.12). Similarly, no association was found in subgroup analysis stratified by ethnicity. Our findings indicated no relationship between IL-1A rs1800587 polymorphism and RA vulnerability.


2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110041
Author(s):  
Guiqin Tan ◽  
Xin Wang ◽  
Guangbing Zheng ◽  
Juan Du ◽  
Fangyu Zhou ◽  
...  

Objective This meta-analysis aimed to determine the associations between the rs3761547, rs3761548, and rs3761549 single-nucleotide polymorphisms (SNPs) of the forkhead box P3 ( FOXP3) gene and susceptibility to Graves’ disease (GD). Methods Case–control studies with information on the associations between the rs3761547, rs3761548, and rs3761549 FOXP3 SNPs and GD published before 01 May 2020 were identified in the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases. Data from the studies were analyzed using RevMan version 5.3. Results Seven independent case–control studies including 4051 GD patients and 4569 controls were included in the meta-analysis. The overall pooled analysis indicated that FOXP3/rs3761548 and FOXP3/rs3761549 polymorphisms were significantly associated with GD susceptibility (rs3761548: A vs. C, odds ratio [OR] = 1.32, 95% confidence interval [CI] 1.05–1.67; rs3761549: TT vs. CC, OR = 1.98, 95%CI 1.49–2.65; (TT + TC) vs. CC, OR = 1.44, 95%CI 1.11–1.88). In contrast, the FOXP3/rs3761547 polymorphism was not associated with GD susceptibility. Subgroup analysis according to ethnicity showed that rs3761548 was associated with GD in Asians but not in Caucasians, whereas rs3761549 was associated in both Asians and Caucasians. Conclusion This meta-analysis demonstrated that FOXP3/rs3761548 and FOXP3/rs3761549 SNPs were significantly associated with susceptibility to GD, at least in Asian populations.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Pengfei Du ◽  
Xiaojie Ma ◽  
Changjiang Wang

Many studies have established that T-lymphocyte antigen-4 (CTLA4) is a susceptible gene for Graves’ disease (GD). Also many studies showed the association between the CTLA4 exon-1 49A/G polymorphism and the risk of developing Graves’ ophthalmopathy (GO) in GD patients. But those results were inconsistent. In recent years many new studies were published which helped to shed light on the relationship of CTLA4 SNP49 with GO. So we performed the meta-analysis to explore the association between the SNP49 and GO susceptibility in GD patients. Studies up to February 29, 2012, were searched by using PubMed. The odds ratio was used to evaluate the strength of the association. Altogether 12 case-control studies involving 2,505 participants were included in the meta-analysis. Results showed that the G allele was related to the increased risk of GO compared with the A allele under allelic genetic model (OR = 1.14, 95% CI: 1.14–1.72,P=0.001) in European subgroup. No publication bias was detected. Our results showed that the SNP49 polymorphism of CTLA4 gene was related to increased risk of GO.


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