Dataset Information

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

ABSTRACT: 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 OR 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.

SUBMITTER: Yuan H

PROVIDER: S-EPMC7036271 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Single nucleotide polymorphism of <i>MTHFR</i> rs1801133 associated with elevated Hcy levels affects susceptibility to cerebral small vessel disease.

Yuan Hongyu H Fu Man M Yang Xianzhang X Huang Kun K Ren Xiaoyan X

PeerJ 20200220

<h4>Background</h4>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 b ...[more]

PMID: 32117640

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Project description:Polymorphisms in MTHFR gene influence risk and overall survival of patients with brain tumor. Global genomic DNA (gDNA) methylation profile from tumor tissues is replicated in peripheral leukocytes. This study aimed to draw a correlation between rs1801133 MTHFR variants, gDNA methylation and overall survival of patients with recurrent glioblastoma (rGBM) under perillyl alcohol (POH) treatment. gDNA from whole blood was extracted using a commercially available kit (Axygen) and quantified by spectrophotometry. Global gDNA methylation was determined by ELISA and rs1801133 polymorphism by PCR-RFLP. Statistical analysis of gDNA methylation profile and rs1801133 variants included Mann-Whitney, Kruskal-Wallis, Spearman point-biserial correlation tests (SPSS and Graphpad Prism packages; significant results for effect size higher than 0.4). Prognostic value of gDNA methylation and rs1801133 variants considered survival profiles at 25?weeks of POH treatment, having the date of protocol adhesion as starting count and death as the final event. Most rGBM patients showed global gDNA hypomethylation (median?=?31.7%) and a significant, moderate and negative correlation between TT genotype and gDNA hypomethylation (median?=?13.35%; rho?=?-?0.520; p?=?0.003) compared to CC variant (median?=?32.10%), which was not observed for CT variant (median?=?33.34%; rho?=?-?0.289; p?=?0.06). gDNA hypermethylated phenotype (median?=?131.90%) exhibited significant, moderate and negative correlations between TT genotype (median?=?112.02%) and gDNA hypermethylation levels when compared to CC (median?=?132.45%; rho?=?-?0,450; p?=?0.04) or CT (median?=?137.80%; rho?=?-?0.518; p?=?0.023) variants. TT variant of rs1801133 significantly decreased gDNA methylation levels for both patient groups, when compared to CC (d values: hypomethylated?=?1.189; hypermethylated?=?0.979) or CT (d values: hypomethylated?=?0.597; hypermethylated?=?1.167) variants. Positive prognostic for rGBM patients may be assigned to gDNA hypermethylation for survivors above 25?weeks of treatment (median?=?88?weeks); and TT variant of rs1801133 regardless POH treatment length. rGBM patients under POH-based therapy harboring hypermethylated phenotype and TT variant for rs1801133 had longer survival. Intranasal POH therapy mitigates detrimental effects of gDNA hypomethylation and improved survival of patients with rGBM harboring TT mutant variant for MTHFR rs1801133 polymorphism. CONEP -9681- 25,000.009267 / 2004. Registered 12th July, 2004.

Dataset Information

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

Publications

Single nucleotide polymorphism of <i>MTHFR</i> rs1801133 associated with elevated Hcy levels affects susceptibility to cerebral small vessel disease.

Similar Datasets

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