A possible synergistic effect of MTHFR C677T polymorphism on homocysteine level variations increased risk for ischemic stroke

Ai-Fan, Li; Shi, Yunshu; Xu, Liyan; Zhang, Yuchao; Zhao, Hang; Li, Qiangmin; Zhao, Xingjuan; Cao, Xinhui; Zheng, Hong; He, Ying

doi:10.1097/md.0000000000009300

Cited by 26 publications

(22 citation statements)

References 20 publications

(18 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Firstly, no obvious heterogeneities were detected in overall analyses for two investigated polymorphisms, which indicated that eligible studies could be considered as homogeneous, and thus synthesize the results of these studies is statistically feasible. Secondly, previous experimental studies have shown that the C to T substitution of rs1801133 (substitution of valine for alanine) and A to C substitution of rs1801131 (substitution of glutamate for alanine) could lead to reduced enzymatic activity and result in hyperhomocysteinemia, which may partially explain our positive findings (Li et al, ; Li, Dai, Zheng, Liu, & Huang, ). Thirdly, the pathogenic mechanism of glaucoma is quite complex, and hence it is unlikely that a single gene polymorphism can significantly contribute to its development.…”

Section: Discussionmentioning

confidence: 68%

Correlation between MTHFR polymorphisms and glaucoma: A meta‐analysis

Chen¹

2019

Molec Gen & Gen Med

View full text Add to dashboard Cite

Background Whether methylenetetrahydrofolate reductase (MTHFR) polymorphisms are implicated in glaucoma remains controversial. Therefore, we performed this study to better assess the relationship between MTHFR polymorphisms and the likelihood of glaucoma. Methods A systematic research of PubMed, Medline, and Embase was performed to retrieve relevant articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results A total of 18 studies with 7,168 participants were analyzed. In overall analyses, a significant association with the likelihood of glaucoma was detected for the rs1801133 polymorphism in dominant (p = 0.04, OR = 0.90, 95%CI 0.81–1.00) and allele (p = 0.02, OR = 0.91, 95%CI 0.84–0.98) comparisons. Further, subgroup analyses by ethnicity revealed that both rs1801131 and rs1801133 polymorphisms were significantly associated with the likelihood of glaucoma in West Asians. However, no positive results were detected for two investigated polymorphisms in East Asians and Caucasians. Conclusion Our findings indicated that rs1801131 and rs1801133 polymorphisms may serve as genetic biomarkers of glaucoma in West Asians.

show abstract

Section: Discussionmentioning

confidence: 68%

Correlation between MTHFR polymorphisms and glaucoma: A meta‐analysis

Chen¹

2019

Molec Gen & Gen Med

View full text Add to dashboard Cite

show abstract

“…Wang et al (2018) found that the SNP of the MTHFR rs1801133 and NAFLD had a potential synergistic effect on elevated Hcy levels. Li et al (2017) found that the plasma Hcy levels of different genotypes of the MTHFR rs1801133 showed the tendency of the TT genotype >CT genotype >CC genotype. They concluded that a possible synergistic effect of the MTHFR rs1801133 SNP on plasma Hcy levels increased the risk of IS.…”

Section: Discussionmentioning

confidence: 94%

“…As a sulfur-containing amino acid, Hcy is an important intermediate product for the metabolism of methionine. Hcy has an important role in vascular function (Li et al, 2017). Elevated Hcy levels can predispose vascular smooth muscle cells and endothelial cells to injury, which leads to activation of coagulation factors, expression of plasminogen activator inhibitor, endothelial proliferation and so on (Hainsworth et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

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

Yuan

Yang

et al. 2020

PeerJ

View full text Add to dashboard Cite

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.

show abstract

“…It is also worth to underline that probable role of MTHFR gene www. journals.viamedica.pl/ginekologia_polska polymorphisms in the etiology of intrauterine fetal death may be a result of hyperhomocysteinemia caused by these genetic variants [24][25][26].…”

Section: Discussionmentioning

confidence: 99%

MTHFR genetic polymorphism and the risk of intrauterine fetal death in Polish women

et al. 2019

View full text Add to dashboard Cite

Objectives:To evaluate the role of MTHFR genetic variants in the etiology of intrauterine fetal death in the second part of pregnancy at women from Polish population. Material and methods:A case-control study was performed on a 76 women with a positive history of at least one intrauterine fetal death after 22 gestational week and 400 healthy controls. The MTHFR genotyping for polymorphic sites 667C > T, 1298A > C, 1793G > A was determined by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) method. Results:For 1298A > C polymorphism, no statistically significant higher frequency of AA vs. AC+CC genotype was observed in the IUFD group 67.1 % vs. 55.2% in the control group (OR = 0.61, p = 0.05, p corr = 0.15). We observed overrepresentation of three-locus haplotype CCG (p = 0.20; p corr = 0.56) and two-locus haplotype CC (p = 0.17; p corr = 0.48) in the IUFD group compared to controls. Conclusions:There was no observed relationships in genotype frequency of MTHFR 677C > T and 1793G > A variants, however 1298A > C showed a slightly higher but statistically insignificant prevalence in IUFD compared to the controls in Polish population. Further studies on a larger population are needed.

show abstract

A possible synergistic effect of MTHFR C677T polymorphism on homocysteine level variations increased risk for ischemic stroke

Cited by 26 publications

References 20 publications

Correlation between MTHFR polymorphisms and glaucoma: A meta‐analysis

Correlation between MTHFR polymorphisms and glaucoma: A meta‐analysis

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

MTHFR genetic polymorphism and the risk of intrauterine fetal death in Polish women

Contact Info

Product

Resources

About