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Differential effects of the methylenetetrahydrofolate reductase polymorphisms (C677T and A1298C) on hematological malignancies among Latinos: a meta-analysis.

ABSTRACT: Our objective was to determine the association between the methylenetetrahydrofolate reductase polymorphisms (C677T and A1298C) and the risk of developing acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), acute myeloid leukemia (AML), and multiple myelomas (MM) in Latinos. PubMed, SCOPUS, EBSCO, LILACS, and other Latin-specific databases were searched for case-control studies that investigated the association between these polymorphisms and hematologic malignancies until November 2017. Genotype distributions were extracted and either fixed-effects or random-effects models were used to calculate the pooled crude odds ratios (ORs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. No publication bias was detected by the Begg-Mazumdar's test and Egger's test. From 290 publications, we identified 15 studies on the C677T polymorphism and 13 studies on the A1298C polymorphism. We observed a significant decrease in risk for the C677T polymorphism (OR range=0.54-0.75, p<0.01) and a significant increase in risk for the A1298C polymorphism (OR range=1.28-2.52, p<0.05) in developing ALL for all genetic models. No associations were determined for CML, AML, or MM for either polymorphism. This meta-analysis demonstrated that the A1298C polymorphism was associated with an increased risk of developing ALL, whereas the C677T polymorphism was associated with a decreased risk (protective factor) in the Latino population.

SUBMITTER: Garcia-Hernandez SC

PROVIDER: S-EPMC6905449 | biostudies-literature | 2019 Jul-Sep

REPOSITORIES: biostudies-literature

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Differential effects of the methylenetetrahydrofolate reductase polymorphisms (C677T and A1298C) on hematological malignancies among Latinos: a meta-analysis.

Garcia-Hernandez Samanta Celeste SC Meneses-Sanchez Perla P Porchia Leonardo Martin LM Torres-Rasgado Enrique E Pérez-Fuentes Ricardo R Gonzalez-Mejia Martha Elba ME

Genetics and molecular biology 20190701 3

Our objective was to determine the association between the methylenetetrahydrofolate reductase polymorphisms (C677T and A1298C) and the risk of developing acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), acute myeloid leukemia (AML), and multiple myelomas (MM) in Latinos. PubMed, SCOPUS, EBSCO, LILACS, and other Latin-specific databases were searched for case-control studies that investigated the association between these polymorphisms and hematologic malignancies until Novemb ...[more]

PMID: 31188929

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Project description:Background18 previous meta-analyses have been published on the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms with male infertility risk. However, results of the previous meta-analyses were still inconsistent. Moreover, their meta-analyses did not assess false-positive report probabilities except one study. Furthermore, many new studies have been published, and therefore an updated meta-analysis and re-analysis of systematic previous meta-analyses were performed to further explore these issues.ObjectivesTo determine the association between MTHFR C677T and A1298C polymorphisms and male infertility risk.MethodsCrude odds ratios and their 95% confidence intervals were used to assess the association between MTHFR C677T and A1298C polymorphisms and male infertility risk. We used the Bayesian false discovery probability (BFDP) to assess the credibility of statistically significant associations.ResultsFifty-nine studies were included concerning the MTHFR C677T and 28 studies were found on the MTHFR A1298C with male infertility risk. Overall, the MTHFR C677T was associated with increased male infertility risk in overall populations, Africans, East Asians, West Asians, South Asians, azoospermia, and Oligoasthenoteratozoospermia (OAT). In further sensitivity analysis and BFDP test, the positive results were only considered as "noteworthy" in the overall population (TT vs CC: BFDP = 0.294, CT + TT vs CC: BFDP = 0.300, T vs C: BFDP = 0.336), East Asians (TT vs CC: BFDP = 0.089, TT vs CT + CC: BFDP = 0.020, T vs C: BFDP < 0.001), West Asians (TT vs CC: BFDP = 0.584), hospital-based studies (TT vs CC: BFDP = 0.726, TT vs CT + CC: BFDP = 0.126), and OAT (TT vs CT + CC: BFDP = 0.494) for MTHFR C677T. In addition, a significantly increased male infertility risk was found in East Asians and population-based studies for MTHFR A1298C. However, we did not find that the positive results were considered as "noteworthy" in the overall and all subgroup analyses for MTHFR A1298C.ConclusionsIn summary, this study indicates that the MTHFR C677T is associated with increased male infertility risk in East Asians, West Asians, and OAT. No significant association was observed on the MTHFR A1298C with male infertility risk.

Project description:BackgroundMethylenetetrahydrofolate reductase, the encoded by the MTHFR gene, plays a crucial role in converting the amino acid homocysteine to methionine. Two polymorphisms of the MTHFR gene, C677T and A1298C, reportedly reduce enzyme activity, resulting in hyperhomocysteinemia. Patients with C677T and A1298C polymorphisms may be at higher risk for developing abnormal hyperhomocysteinemia, which has been linked to catastrophic neurological including fatal outcomes.ObjectiveDetermine the prevalence of the MTHFR gene variants C677T and A1298C among pediatric dental patients treated at King Abdulaziz University Hospital.DesignCross-sectional.SettingClinics of pediatric dentistry department.Subjects and methodsHealthy Saudi children 6-12 years old with no known allergies were screened for eligibility between May and December 2019. A single investigator collected saliva samples. The MTHFR C677T and A1298C polymorphisms were analyzed using polymerase chain reaction and restriction fragment length polymorphism.Main outcome measureThe prevalence of MTHFR gene variants (C677T and A1298C) among the subjects.Sample size138.ResultsMTHFR C677T polymorphism was present in 36.2% of the sample and 90.0% of children carrying this allele were heterozygotes. MTHFR A1298C polymorphism was present in 91.3% of the sample and 77.0% of the children carrying this allele were heterozygotes. No linkage disequilibrium between MTHFR C677T and MTHFR A1298C was observed within this sample.ConclusionsOur study found a high frequency of the MTHFR A1298C genotype, which was substantially more abundant than expected based on a Hardy-Weinberg distribution. Therefore, caution is advised in using N2O in Saudi children as the increased prevalence of this MTHFR allele may increase the incidence of serious adverse effects among these children.LimitationsFurther studies are recommended with a larger sample size from randomly selected hospitals from different regions of Saudi Arabia.Conflict of interestNone.

Dataset Information

Differential effects of the methylenetetrahydrofolate reductase polymorphisms (C677T and A1298C) on hematological malignancies among Latinos: a meta-analysis.

Publications

Differential effects of the methylenetetrahydrofolate reductase polymorphisms (C677T and A1298C) on hematological malignancies among Latinos: a meta-analysis.

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