Single nucleotide polymorphism of MTHFR rs1801133 associated with elevated Hcy levels affects susceptibility to cerebral small vessel disease

PeerJ

article

Hongyu Yuan¹  Man Fu²  Xianzhang Yang¹  Kun Huang¹  Xiaoyan Ren¹ 

[1] The Third Department of Neurology, Heze Municipal Hospital, Heze, Shandong Province;Department of Neurology, The Third People’s Hospital of Heze, Heze, Shandong Province

关键词: Methylenetetrahydrofolate reductase;    Single nucleotide polymorphism;    Homocysteine;    Cerebral small vessel disease;   

DOI  :  10.7717/peerj.8627

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundMethylenetetrahydrofolate reductase (MTHFR) is indispensable for the conversion of homocysteine (Hcy) to methionine. The single nucleotide polymorphism (SNP) of MTHFR gene (rs1801133, C667T) is correlated with decreased enzyme activity that eventually results in elevated plasma Hcy levels. Hyperhomocysteinemia has been confirmed to be involved in the pathogenesis of stroke, cerebral small vessel disease (CSVD), various metabolic disorders and so on. However, the relationship between the MTHFR gene polymorphisms, Hcy, and CSVD has not been investigated. In this study, the relationship between SNPs of MTHFR gene and CSVD was determined after adjusting for cardiovascular risk factors, and the potential mechanism based on Hcy levels was explored.MethodsA total of 163 consecutive CSVD patients were collected as the case group. In the corresponding period, 326 healthy people were selected as the control group, who were matched to these cases according to age (±2 years) and gender at a ratio of 2:1. SNPs of MTHFR rs1801133, rs1801131, rs2274976, rs4846048, rs4846049, rs13306561 and rs3737964, were genotyped with TaqMan Pre-Designed SNP Genotyping Assays. Plasma Hcy levels were detected using Hcy reagent through enzymatic cycling assay. Multivariate analysis was used to identify the SNPs associated with CSVD susceptibility. Plasma Hcy levels were compared between different genotypes.ResultsThe MTHFR rs1801133 TT and CT genotype had increased risk for CSVD, and the OR CC genotype (19.91 ± 8.73 pg/ml vs 17.04 ± 5.68 pg/ml vs 14.96 ± 4.85 pg/ml).ConclusionsThe SNP of MTHFR rs1801133 was correlated with CSVD, and the TT and CT genotypes had increased risk for CSVD compared to the CC genotype. The potential mechanism was associated with elevated Hcy levels.

【 授权许可】

CC BY