The SNP Rs915014 in MTHFR Regulated by MiRNA Associates with Atherosclerosis

• Main Authors: Xinye Liu, Lingxu Wang, Hao Chi, Jin Wang, Qian Zheng, Jingye Li, Yong Li, Dongwei Yang
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2018-02-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Atherosclerosis; MTHFR; Bioinformatics; Homocysteine; MiR-2861
• Online Access: https://www.karger.com/Article/FullText/487355

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.