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Associations of the MTHFR rs1801133 polymorphism with coronary artery disease and lipid levels: a systematic review and updated meta-analysis.
Luo, Z, Lu, Z, Muhammad, I, Chen, Y, Chen, Q, Zhang, J, Song, Y
Lipids in health and disease. 2018;(1):191
Abstract
BACKGROUND The associations of the 5,10-methylenetetrahydrofolate reductase gene (MTHFR) rs1801133 polymorphism with coronary artery disease (CAD) and plasma lipid levels have been widely investigated, but the results were inconsistent and inconclusive. This meta-analysis aimed to clarify the relationships of the rs1801133 polymorphism with CAD and plasma lipid levels. METHODS By searching in PubMed, Google Scholar, Web of Science, Cochrane Library, Wanfang, VIP and CNKI databases, 123 studies (87,020 subjects) and 65 studies (85,554 subjects) were identified for the CAD association analysis and the lipid association analysis, respectively. Odds ratio (OR) and standardized mean difference (SMD) were used to determine the effects of the rs1801133 polymorphism on CAD risk and lipid levels, respectively. RESULTS The variant T allele of the rs1801133 polymorphism was associated with increased risk of CAD under allelic model [OR = 1.11, 95% confidence interval (CI) = 1.06-1.17, P < 0.01], additive model (OR = 1.25, 95% CI = 1.14-1.37, P < 0.01), dominant model (OR = 1.11, 95% CI = 1.04-1.17, P < 0.01), and recessive model (OR = 1.22, 95% CI = 1.12-1.32, P < 0.01). The T carriers had higher levels of total cholesterol (TC) (SMD = 0.04, 95% CI = 0.01-0.07, P = 0.02) and low-density lipoprotein cholesterol (LDL-C) (SMD = 0.07, 95% CI = 0.01-0.12, P = 0.01) than the non-carriers. CONCLUSIONS The meta-analysis suggested that the T allele of the rs1801133 polymorphism is a risk factor for CAD, which is possibly and partly mediated by abnormal lipid levels.
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The association between methionine synthase A2756G polymorphism and hematological cancer: A meta-analysis.
Wu, B, Liu, K, Yang, JP, Hu, Y, Zhang, J, He, JX
Medicine. 2017;(48):e7469
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Abstract
BACKGROUND Numerous studies have focused on the association of methionine synthase (MS) A2756G polymorphism and acute hematological cancer risk. However, the results remain inconsistent. Therefore, a meta-analysis was performed to derive a more precise estimate of the association between them. METHODS This meta-analysis involved 25 articles (26 studies) including 8641 hematological cancer patients and 15,498 controls. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) of the association between MS A2756G polymorphism and the risk of hematological cancer were calculated. RESULTS Overall, no significant increased risks were found between MS A2756G polymorphism and hematological cancer risk under allelic homozygote (GA vs AA: OR = 0.98, 95% CI = 0.89-1.07, P = .62), heterozygote (GG vs AA: OR = 0.99, 95% CI = 0.85-1.15, P = .91), dominant (AG+GG vs AA: OR = 0.99, 95% CI = 0.90-1.08, P = .93), and recessive (GG vs AG+AA: OR = 1.00, 95% CI = 0.86-1.16, P = .97) models, respectively. In the stratified analyses by ethnicity and source of controls, there were still no significant associations between them in all genetic models. CONCLUSIONS Therefore, these findings demonstrate that MS A2756G polymorphism may not be a risk factor for hematological cancer.
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Association between rs1344706 of ZNF804A and schizophrenia: a meta-analysis.
Zhu, M, Liu, T, Zhang, J, Jia, S, Tang, W, Luo, Y
Genomics, proteomics & bioinformatics. 2014;(6):292-6
Abstract
Schizophrenia is one of the most serious mental diseases found in humans. Previous studies indicated that the single nucleotide polymorphism (SNP) rs1344706 in the gene ZNF804A encoding zinc finger protein 804A was associated with schizophrenia in Caucasian population but not in Chinese Han population. However, current results are conflicting in Asian population. In the present study, a meta-analysis was performed to revisit the association between rs1344706 and the risk of schizophrenia in Asian, Caucasian and other populations. Electronic search of PubMed database identified 25 case-control studies with available genotype frequencies of rs1344706 for the meta-analysis, involving a total of 15,788 cases and 22,654 controls. A pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the association. The current meta-analysis showed an association between rs1344706 and schizophrenia in Caucasian populations (P=0.028, OR=1.138, 95% CI: 1.014-1.278; P=0.004 for heterogeneity) and Asian populations (P=0.008, OR=1.092, 95% CI: 1.023-1.165; P=0.001 for heterogeneity), but not in other populations (P=0.286, OR=1.209, 95% CI: 0.853-1.714, P=0.120 for heterogeneity). Egger's test (P>0.05) and Begg's test (P>0.05) are both suggestive of the lack of publication bias for the included studies. Thus, the absence of association in other populations suggests a genetic heterogeneity in the susceptibility of schizophrenia and demonstrates the difficulties in replicating genome-wide association study findings regarding schizophrenia across different ethnic populations. To validate the association between rs1344706 and schizophrenia, further studies with larger participant populations worldwide are needed.
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5,10-Methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTRR), and methionine synthase reductase (MTR) gene polymorphisms and adult meningioma risk.
Zhang, J, Zhou, YW, Shi, HP, Wang, YZ, Li, GL, Yu, HT, Xie, XY
Journal of neuro-oncology. 2013;(2):233-9
Abstract
The causes of meningiomas are not well understood. Folate metabolism gene polymorphisms have been shown to be associated with various human cancers. It is still controversial and ambiguous between the functional polymorphisms of folate metabolism genes 5,10-methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTRR), and methionine synthase reductase (MTR) and risk of adult meningioma. A population-based case–control study involving 600 meningioma patients (World Health Organization [WHO] Grade I, 391 cases; WHO Grade II, 167 cases; WHO Grade III, 42 cases) and 600 controls was done for the MTHFR C677T and A1298C, MTRR A66G, and MTR A2756G variants in Chinese Han population. The folate metabolism gene polymorphisms were determined by using a polymerase chain reaction–restriction fragment length polymorphism assay. Meningioma cases had a significantly lower frequency of MTHFR 677 TT genotype [odds ratio (OR) = 0.49, 95 % confidence interval (CI) 0.33–0.74; P = 0.001] and T allele (OR = 0.80, 95 % CI 0.67–0.95; P = 0.01) than controls. A significant association between risk of meningioma and MTRR 66 GG (OR = 1.41, 95 % CI 1.02–1.96; P = 0.04) was also observed. When stratifying by the WHO grade of meningioma, no association was found. Our study suggested that MTHFR C677T and MTRR A66G variants may affect the risk of adult meningioma in Chinese Han population.
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The Arg194Trp polymorphism in the XRCC1 gene and cancer risk in Chinese Mainland population: a meta-analysis.
Huang, J, Zhang, J, Zhao, Y, Liao, B, Liu, J, Li, L, Liao, M, Wang, L
Molecular biology reports. 2011;(7):4565-73
Abstract
The Arg194Trp polymorphism in the X-ray repair cross-complementing group 1 (XRCC1) gene has been proved to be in association with cancer risk in Chinese Mainland population, but a large number of studies have reported inconclusive results. A more comprehensive and precise estimation of the relationship is needed to clear the way towards future studies. Thus, we performed a meta-analysis to analysis these associations. A total of 34 case-control studies in 34 articles were included in this meta-analysis. The results showed that the 194Trp/Trp homozygote had a 31% increased risk of cancer than 194Trp/Arg and 194Arg/Arg genotypes, OR was 1.31 and 95%CI was 1.13 to 1.53. In the subgroup analysis by cancer sites, the Arg194Trp polymorphism was associated with increased risks of lung cancer (OR = 1.27 and 95%CI: 1.07-1.50 for Trp/Trp versus Arg/Arg + Arg/Trp) and esophageal cancer (OR = 1.68 and 95%CI: 1.33-2.13 for Trp/Trp versus Arg/Arg + Arg/Trp). This meta-analysis suggested that the Arg194Trp polymorphism of the XRCC1 gene is a cancer susceptible factor among Chinese Mainland population. More intensive and deeper studies are needed to further reveal the mechanism between Arg194Trp polymorphisms of XRCC1 gene and cancer risks in Chinese Mainland population.
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Methionine synthase A2756G polymorphism and cancer risk: a meta-analysis.
Yu, K, Zhang, J, Zhang, J, Dou, C, Gu, S, Xie, Y, Mao, Y, Ji, C
European journal of human genetics : EJHG. 2010;(3):370-8
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Abstract
Polymorphisms in methionine synthase (MTR) gene may be involved in carcinogenesis by affecting DNA methylation. However, association studies on MTR A2756G polymorphism in cancers have reported conflicting results. Therefore we performed a meta-analysis to better assess the associations. A total of 24 896 cancer patients and 33 862 controls from 52 articles for MTR A2756G were investigated. Overall, individuals carrying MTR 2756GG genotype had a subtly reduced cancer risk under a recessive genetic model (odds ratio (OR), 0.92; P=0.053; 95% confidence interval (95% CI), 0.84-1.00; I(2)=0.0%; P(heterogeneity)=0.61). In the subgroup analyses by ethnicity, 2756GG was associated with a significantly reduced cancer risk in European populations (OR, 0.83; P=0.001; 95% CI, 0.74-0.93; I(2)=0.0%; P(heterogeneity)=0.99). However, in Asian populations, a significantly elevated association between 2756GG genotype and cancer risk was observed (OR, 1.33; P=0.012; 95% CI, 1.06-1.65; I(2)=0.0%; P(heterogeneity)=0.50). In studies stratified by tumor site, there was a significantly reduced risk of acute lymphoblastic leukemia (ALL) (OR, 0.54; P=0.049; 95% CI, 0.29-1.00; I(2)=10.7%; P(heterogeneity)=0.33) and colorectal cancer (OR, 0.63; P=0.004; 95% CI, 0.47-0.87; I(2)=0.0%; P(heterogeneity)=0.73) in European populations. Our study indicates that MTR A2756G polymorphism is a candidate gene polymorphism for cancer susceptibility regardless of environmental factors. Large-scale, well-designed, and population-based studies are required to further investigate gene-gene and gene-environment interactions on MTR A2756G polymorphism and tissue-specific cancer risk in an ethnicity-specific population.