与同型半胱氨酸水平升高相关的rs1801133单核苷酸多态性影响脑小血管病的易感性。
Single nucleotide polymorphism of rs1801133 associated with elevated Hcy levels affects susceptibility to cerebral small vessel disease.
作者信息
Yuan Hongyu, Fu Man, Yang Xianzhang, Huang Kun, Ren Xiaoyan
机构信息
The Third Department of Neurology, Heze Municipal Hospital, Heze, Shandong Province, China.
Department of Neurology, The Third People's Hospital of Heze, Heze, Shandong Province, China.
出版信息
PeerJ. 2020 Feb 20;8:e8627. doi: 10.7717/peerj.8627. eCollection 2020.
BACKGROUND
Methylenetetrahydrofolate 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.
METHODS
A 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.
RESULTS
The MTHFR rs1801133 TT and CT genotype had increased risk for CSVD, and the was higher in the TT genotype than in the CT genotype (2.307 vs 1.473). The plasma Hcy levels of different genotypes showed the tendency of the TT genotype > CT genotype > CC genotype (19.91 ± 8.73 pg/ml vs 17.04 ± 5.68 pg/ml vs 14.96 ± 4.85 pg/ml).
CONCLUSIONS
The 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.
背景
亚甲基四氢叶酸还原酶（MTHFR）对于同型半胱氨酸（Hcy）转化为蛋氨酸至关重要。MTHFR基因的单核苷酸多态性（SNP）（rs1801133，C667T）与酶活性降低相关，最终导致血浆Hcy水平升高。高同型半胱氨酸血症已被证实与中风、脑小血管病（CSVD）、各种代谢紊乱等的发病机制有关。然而，MTHFR基因多态性、Hcy与CSVD之间的关系尚未得到研究。在本研究中，在调整心血管危险因素后确定了MTHFR基因SNP与CSVD之间的关系，并探讨了基于Hcy水平的潜在机制。
方法
共收集163例连续的CSVD患者作为病例组。在同一时期，选择326名健康人作为对照组，根据年龄（±2岁）和性别以2:1的比例与这些病例进行匹配。使用TaqMan预设计SNP基因分型检测法对MTHFR rs1801133、rs1801131、rs2274976、rs4846048、rs4846049、rs13306561和rs3737964的SNP进行基因分型。通过酶循环法使用Hcy试剂检测血浆Hcy水平。采用多变量分析确定与CSVD易感性相关的SNP。比较不同基因型之间的血浆Hcy水平。
结果
MTHFR rs1801133的TT和CT基因型患CSVD的风险增加，TT基因型的该风险高于CT基因型（2.307对1.473）。不同基因型的血浆Hcy水平呈现TT基因型>CT基因型>CC基因型的趋势（19.91±8.73 pg/ml对17.04±5.68 pg/ml对14.96±4.85 pg/ml）。
结论
MTHFR rs1801133的SNP与CSVD相关，与CC基因型相比，TT和CT基因型患CSVD的风险增加。潜在机制与Hcy水平升高有关。
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