scholarly journals The C677T polymorphism of the methylenetetrahydrofolate reductase gene and susceptibility to late-onset Alzheimer’s disease

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 32-40 ◽  
Author(s):  
Jian Yi ◽  
Lan Xiao ◽  
Sheng-Qiang Zhou ◽  
Wen-Jiang Zhang ◽  
Bai-Yan Liu

AbstractFolate metabolism makes a crucial contribution towards late-onset Alzheimer’s disease (LOAD). Moreover, methylenetetrahydrofolate reductase (MTHFR) constitutes the primary enzyme of the folate pathway. We hypothesize that there is an association of C677T polymorphism in the MTHFR gene with the susceptibility to LOAD. Previous published research has investigated the link between the MTHFR C677T polymorphisms and LOAD susceptibility; nevertheless, the findings have continued to be not only controversial, but also indecisive. Accordingly, we carried out the present meta-analysis for the assessment of the potential link that exists between the MTHFR C677T polymorphism and the susceptibility to LOAD. Furthermore, we carried out a literature search of the PubMed, EMBASE, Cochrane Library, and WanFang database up to August 10, 2018. The odds ratios (ORs) with the respective 95% confidence interval (95%CI) were put to use for the evaluation of the robustness of the link of the MTHFR C677T polymorphism with the vulnerability to LOAD. All statistical analyses were carried out using STATA 15.0. An aggregate of 14 case-control research works was retrieved, involving 2,467 LOAD patients as well as 2,877 controls. We found that a substantial link exists between C677T polymorphism and LOAD risk in a codominant framework (TC vs. CC: OR=1.22, 95%CI=1.00-1.49, P=0.049). In addition to the stratified analysis based on ethnicity, which suggested that C677T polymorphism was likely linked only to an augmented threat of LOAD in Asians, it did not exist among Caucasians. Furthermore, in the subgroup analysis carried out using APOE ɛ4 status, a substantial increase in the susceptibility to LOAD was detected in APOE ɛ4 carriers as well as non-APOE ɛ4 carriers. In sum, the current meta-analysis revealed that MTHFR C677T polymorphism was associated with susceptibility to LOAD. Further extensive case-control studies are required.

2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Miao Gao ◽  
Na Feng ◽  
Meixia Zhang ◽  
Xinyu Ti ◽  
Xiuping Zuo

Abstract Recent years, it is a highly debated topic that whether methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and A1298C polymorphism could increase susceptibility to venous thromboembolism (VTE) in the Asian and Caucasian. Therefore, we expect to settle that controversy evidentially. Basic methods: Electronic databases (Pubmed, embase, Cochrane library, scopus, OvidSP, Wiley Online library, Springer link, EBSCO, Elsevier Science Direct, Google scholar) without date limitation were searched. Crude odds ratio (OR) along with 95% confidence interval (95% CI) was calculated to assess the association quantitatively. Finally, a total of 37 eligible studies were included, containing 31 for MTHFR C677T polymorphism and 6 for MTHFR A1298C polymorphism. The pooled results suggested that MTHFR C677T mutation may increase susceptibility to VTE in reverse recessive model (CC+CT vs TT): OR = 0.68 (0.56, 0.83), reverse dominant model (CC vs CT +TT): OR = 0.82 (0.72, 0.94), heterozygote model (CT vs TT): OR = 0.65 (0.52, 0.81), homozygote model (CC vs TT): OR = 0.73 (0.60, 0.89) and allele model (C vs T): OR = 0.80 (0.71, 0.90). Subgroup analysis about Asian also support that results, but Caucasian group not. In addition, MTHFR A1298C polymorphism may be not related to VTE in all genetic model. The results of meta-analysis indicated that MTHFR C677T polymorphism might increase the risk of VTE, especially in Asian population.


2020 ◽  
Author(s):  
Vandana Rai ◽  
Pradeep Kumar

AbstractPolycystic ovary syndrome (PCOS) is the most common form of endocrinopathy of women. Several studies have investigated the association of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with PCOS risk but the results are contradictory. So, the aim of the present study was to carry out a meta-analysis of a published case control studies to find out exact association between MTHFR gene C677T polymorphism and PCOS susceptibility. Pubmed, Springer link, Science Direct and Google Scholar databases were searched for case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) was used as association measure and meta-analysis was performed using MIX and MetaAnalyst programs.Meta-analysis of 24 studies showed strong significant association between C677T polymorphism and PCOS risk (for T vs. C: OR= 1.18, 95% CI=1.01-1.38, p=0.03; for TT vs. CC: OR= 1.37, 95% CI=1.0-1.89, p= 0.045; for TT + CT vs. CC: OR= 1.31, 95% CI= 1.07-1.62, p= 0.008; for CT vs. CC: OR= 1.31, 95% CI= 1.04-1.62, p= 0.01 and for TT vs. CT + CC: OR= 1.10, 95% CI= 0.82-1.47, p= 0.04). In subgroup analysis, MTHFR C677T polymorphism is significantly associated with PCOS risk with Asian individuallas but in Caucasian population MTHFR C677T polymorphism was not significantly associated with PCOS risk. In conclusion, C677T polymorphism is a risk factor for PCOS.


2021 ◽  
pp. 1-10
Author(s):  
Wei Qin ◽  
Wenwen Li ◽  
Qi Wang ◽  
Min Gong ◽  
Tingting Li ◽  
...  

Background: The global race-dependent association of Alzheimer’s disease (AD) and apolipoprotein E (APOE) genotype is not well understood. Transethnic analysis of APOE could clarify the role of genetics in AD risk across populations. Objective: This study aims to determine how race and APOE genotype affect the risks for AD. Methods: We performed a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library since 1993 to Aug 25, 2020. A total of 10,395 reports were identified, and 133 were eligible for analysis with data on 77,402 participants. Studies contained AD clinical diagnostic and APOE genotype data. Homogeneous data sets were pooled in case-control analyses. Odds ratios and 95% confidence intervals for developing AD were calculated for populations of different races and APOE genotypes. Results: The proportion of APOE genotypes and alleles differed between populations of different races. Results showed that APOE ɛ4 was a risk factor for AD, whereas APOE ɛ2 protected against it. The effects of APOE ɛ4 and ɛ2 on AD risk were distinct in various races, they were substantially attenuated among Black people. Sub-group analysis found a higher frequency of APOE ɛ4/ɛ4 and lower frequency of APOE ɛ3/ɛ3 among early-onset AD than late-onset AD in a combined group and different races. Conclusion: Our meta-analysis suggests that the association of APOE genotypes and AD differ between races. These results enhance our understanding of APOE-related risk for AD across race backgrounds and provide new insights into precision medicine for AD.


2017 ◽  
Vol 56 (4) ◽  
pp. 1451-1457 ◽  
Author(s):  
Andrea Stoccoro ◽  
Pierpaola Tannorella ◽  
Maria Grazia Salluzzo ◽  
Raffaele Ferri ◽  
Corrado Romano ◽  
...  

2020 ◽  
Author(s):  
Vandana Rai ◽  
Pradeep Kumar

AbstractAlcohol dependence is a complex neuropsychiatric disorder. Numerous studies investigated association between MTHFR gene C677T polymorphism and alcohol dependence (AD), but the results of this association remain conflicting. Accordingly, authors conducted a meta-analysis to further investigate such an association. PubMed, Elsevier Science Direct and Springer Link databases were searched for studies on the association between the MTHFR C677T polymorphism and AD. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using the fixed- or random-effects model. Statistical analysis was performed with the software program MetaAnayst and MIX.A total of 11 articles were identified through a search of electronic databases, up to February 28, 2020. The results of the present meta-analysis did not show any association between MTHFR C677T polymorphisms and AD risk (for T vs. C: OR = 1.04, 95% CI = 0.88-1.24; CT vs. CC: OR=1.02, 95%CI= 0.62-1.68; for TT + CT vs. CC: OR = 1.10, 95% CI = 0.94-1.29; for TT vs. CC: OR = 1.01, 95% CI = 0.66-1.51; for TT vs. CT + CC: OR = 0.97, 95% CI = 0.66-1.40). Results of subgroup analysis showed no significant association between MTHFR C677T polymorphism with AD in Asian as well as in Caucasian population. In conclusion, C677T polymorphism is not a risk factor for alcohol dependence.


2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Lingyan Xu ◽  
Zhiqiang Qin ◽  
Feng Wang ◽  
Shuhui Si ◽  
Lele Li ◽  
...  

The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and colorectal cancer (CRC) susceptibility has been researched in numerous studies. However, the results of these studies were controversial. Therefore, the objective of this meta-analysis was to offer a more convincible conclusion about such association with more included studies. Eligible studies published till May 1, 2017 were searched from PubMed, Embase, Web of Science, and CNKI database about such association. Pooled odds ratios (ORs) together with 95% confidence intervals (CIs) were calculated to evaluate such association. And the Begg’s funnel plot and Egger’s test were applied to assess the publication bias. This meta-analysis contained 37049 cases and 52444 controls from 87 publications with 91 eligible case–control studies. Because of lack of data for a particular genotype in several studies, all the included studies were analysed barely in the dominant model. Originally, there was no association between MTHFR C677T polymorphism and CRC susceptibility (OR =0.99, 95% CI =0.94–1.05). After excluding 13 studies according to their heterogeneity and publication bias, rs1801133 polymorphism was found to reduce the risks of CRC significantly (OR =0.96, 95% CI =0.94–0.99). In the subgroup analysis of ethnicity, there was a significant association in Asians (OR =0.94, 95% CI =0.89–1.00). Furthermore, when stratified by the source of controls and genotyping methods, the positive results were observed in population-based control group (OR =0.97, 95% CI =0.93–1.00) and PCR-restriction fragment length polymorphism (PCR-RFLP) method (OR =0.95, 95% CI =0.91–0.99. The results of the meta-analysis suggested that MTHFR C677T polymorphism was associated with CRC susceptibility, especially in Asian population.


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