Meta-analysis of the relationship between methylenetetrahydrofolate reductase C677T and A1298C polymorphism and venous thromboembolism in the Caucasian and Asian.

Xinyu Ti,Xiuping Zuo,Meixia Zhang,Miao Gao,Na Feng

doi:10.1042/bsr20200860

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.

Highlights

Venous thromboembolism (VTE) is a common clinical vascular syndrome, consisting of deep vein thrombosis (DVT) and pulmonary embolism (PE), which are two different forms of the same disease [1] At present, venous thrombosis has become the third cause of cardiovascular disease and common complications of cancer, such as lung cancer [2]
There are 32 eligible studies meeting to our inclusion criteria [4,5,7–36], including 31 papers for Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism [4,5,7–25,27–36] and 6 papers for MTHFR A1298C polymorphism [12,15,19,21,26,30]
Some meta-analysis about the relationship between the risk of VTE and MTHFR mutation have been reported, but the objects are mainly limited to C677T and Chinese

Summary

Introduction

Venous thromboembolism (VTE) is a common clinical vascular syndrome, consisting of deep vein thrombosis (DVT) and pulmonary embolism (PE), which are two different forms of the same disease [1] At present, venous thrombosis has become the third cause of cardiovascular disease and common complications of cancer, such as lung cancer [2]. VTE is a complex multi-factor disease, in which gene mutation plays an important role [3]. There are great ethnic and regional characteristics of gene mutation in VTE. Exploring the susceptible genes to provide the basis for the prevention and treatment of VTE will be one of the important research directions of comprehensive therapy for vascular diseases and cancer. Methylenetetrahydrofolate reductase (MTHFR) is a homocysteine (Hey) metabolic regulatory enzyme. It could reduce N5, N10-methylene tetrahydro folic acid to N5- methyl tetrahydro folic acid, and the latter has the ability to maintain the stability of plasma Hey. The decrease of MTHFR activity will give rise to impaired Hey methylation and further hyperhomocysteinemia, which could destroy vascular endothelium

Methods

Results

Conclusion