Abstract

BackgroundThe geographical and ethnic distributions of the polymorphic methylenetetrahydrofolate reductase (MTHFR) mutations (C677T and A1298C) and methionine synthase reductase (MTRR) mutation (A66G) remain heterogeneous in China. The goal of this study was to estimate the pooled frequencies of the alleles and associated genotypes of these gene polymorphisms among healthy populations in Mainland China.Objective and MethodsWe systematically reviewed published epidemiological studies on the distributions of 3 genetic variants in Chinese healthy populations living in Mainland China through a meta-analysis. The relevant electronic databases were searched. All of the raw data of the eligible citations were extracted. The frequency estimates were stratified by geography, ethnicity and sex.ResultsSixty-six studies were identified with a total of 92277 study participants. The meta-analysis revealed that the frequencies of the MTHFR C677T, A1298C, and MTRR A66G gene polymorphisms varied significantly between different ethnic groups and along geographical gradients. The frequencies of the 677T allele and 677TT genotype increased along the southern-central-northern direction across Mainland China (all Pvalues≤0.001). The frequencies of the 1298C, 1298CC, 66G and 66GG genotypes decreased along the south-central-north direction across the country (all Pvalues≤0.001).ConclusionsOur meta-analysis strongly indicates significant geographical and ethnic variations in the frequencies of the C677T, A1298C, and A66G gene polymorphisms in the folate metabolism pathway among Chinese populations.

Highlights

  • Multiple epidemiological studies have demonstrated that homocysteine is an important biomarker with biological functions in the folate metabolism pathway

  • The meta-analysis revealed that the frequencies of the methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C, and MTRR A66G gene polymorphisms varied significantly between different ethnic groups and along geographical gradients

  • Our meta-analysis strongly indicates significant geographical and ethnic variations in the frequencies of the C677T, A1298C, and A66G gene polymorphisms in the folate metabolism pathway among Chinese populations

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Summary

Introduction

Multiple epidemiological studies have demonstrated that homocysteine is an important biomarker with biological functions in the folate metabolism pathway. Mutations in some key genes encoding homocysteine-metabolizing enzymes, such as methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C and methionine synthase reductase (MTRR) A66G, may contribute to the risk of the development of hyperhomocysteinemia and leas to clinical disorders [6]. Genome-wide association studies (GWASs) have confirmed the association between the MTHFR C677T genotype and homocysteine levels in healthy populations [8]. Along with those investigations, several studies have proposed that double 677CT/1298AC heterozygosity can result in a reduction in enzymatic activity that represents an important risk factor for congenital anomalies, in patients with low blood folate and vitamin B12 concentrations [9].

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