The SNP Rs915014 in MTHFR Regulated by MiRNA Associates with Atherosclerosis

Abstract

Background/Aims: The association between the genetic polymorphisms located in either the exon or untranslated region of MTHFR and the risk of human atherosclerosis has been well-documented. This study analyzed MTHFR polymorphisms at the 3’-untranslated region for association with risk and outcome of atherosclerosis in a Chinese Han population. Methods: The hospital based case-control study was conducted with 500 patients and 600 healthy volunteers as control enrolled. The genotyping was conducted by using Taqman probe. The potential interaction was predicted by multiple bioinformatics analysis. The relative expression of MTHFR was detected by qRT-PCR. Further confirmation was determined by dual-luciferase assay. The plasma homocysteine levels were assayed by ELISA. Results: Cigarette smoking, alcohol consumption, diabetes, hypertension and low levels of serum high-density lipoprotein-C were associated with an increased risk of developing ischemic stroke. MTHFR rs915014 AG and GG genotypes were significantly associated with increased risk of rs915014 compared with the GG genotype. The qRT-PCR confirmed that MTHFR rs915014 AG or GG genotypes could facilitate miR-2861 binding leading to decreased MTHFR levels in cells. In addition, patients carrying the MTHFR rs915014 AG or GG genotypes were associated with accumulation of circulating tHcy volume and a poor atherosclerosis consequence. Conclusions: This study demonstrates that the MTHFR rs915014 is associated with increased risk of atherosclerosis and might be a shot term outcome biomarker for atherosclerosis patients.

Association of Methylenetetrahydrofolate Reductase, Vitamin D Receptor, and Interleukin-16 Gene Polymorphisms With Renal Cell Carcinoma Risk

“…The MTHFR, a critical enzyme in the metabolism of folic acid, converts 5, 10-methylenetetrahydrofolate acid into 5-methyltetrahydrofolate and is a key importance for the homocysteine metabolism. 31,32 The active form of vitamin D acts as a steroid hormone and binds to the VDR. Vitamin D receptor mediates many genomic and nongenomic effects of vitamin D. 33 This receptor is expressed in most cell types including cells in kidney.…”

Increased expression of hub gene CXCL10 in peripheral blood mononuclear cells of patients with systemic lupus erythematosus

“…Furthermore, polymorphisms in CXCL10 determine the secretion of the chemokine by monocyte-derived DCs upon exposure to Aspergillus fumigatus , and are closely associated with the risk of invasive aspergillosis after allogeneic stem-cell transplantation (44). Numerous studies on the function of genes have focused on the binding of micro (mi)RNA with SNPs of their target gene (47,48). In addition, it is well known that miRNAs inhibit the translation of their corresponding mRNA by directly binding to their 3′UTR, so it may be hypothesized that SNPs at the 3′UTR of CXCL10 are associated with its expression.…”

A Genetic Variant of miR-34a Contributes to Susceptibility of Ischemic Stroke Among Chinese Population

“…MTHFR is a key enzyme which plays an important role in the metabolism of homocysteine. A lower expression level of MTHFR causes accumulation of homocysteine, and then results in a higher level of homocysteine (Moll and Varga, 2015; He W. et al, 2017; Liu et al, 2018). According to research conducted by Zhang et al (2015), as a member of the miR-34 family, miR-34b may influence the serum level of homocysteine by binding the 3′-UTR of MTHFR mRNA.…”