Association of a miR-34b binding site single nucleotide polymorphism in the 3'-untranslated region of the methylenetetrahydrofolate reductase gene with susceptibility to male infertility

Zhang, W; Wq, Lin; Hf, Cao; Cy, Li; F, Li

doi:10.4238/2015.october.9.8

Cited by 10 publications

(5 citation statements)

References 40 publications

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“…A lower expression level of MTHFR causes accumulation of homocysteine, and then results in a higher level of homocysteine (Moll and Varga, 2015; He W. et al, 2017; Liu et al, 2018). According to research conducted by Zhang et al (2015), as a member of the miR-34 family, miR-34b may influence the serum level of homocysteine by binding the 3′-UTR of MTHFR mRNA. After predicting the potential targets of miR-34a by software Targetscan, we found that MTHFR was also a potential target of miR-34a.…”

Section: Discussionmentioning

confidence: 99%

A Genetic Variant of miR-34a Contributes to Susceptibility of Ischemic Stroke Among Chinese Population

et al. 2019

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miRNAs are small non-coding RNAs modulating gene expression, and variants in miRNA genes are involved in the pathogenesis of ischemic stroke (IS). However, the effect of miR-34a polymorphisms on IS susceptibility has rarely been reported. In the present study, we investigated the association between rs12128240, rs2666433, and rs6577555 of the miR-34a gene and IS susceptibility. Snapshot assay was used to detect miR-34a polymorphisms in 548 IS patients and 560 controls. Relative expression of miR-34a was measured by quantitative real-time PCR. We found that rs2666433 was associated with a significantly increased risk of IS (AA vs. GG: OR = 1.61, 95% CI = 1.05–2.52, P = 0.031; AA vs. GG+GA: OR = 1.58, 95% CI = 1.05–2.45, P = 0.026). For the IS subtypes, rs2666433 was associated with large artery atherosclerosis (AA vs. GG: OR = 2.09, 95% CI = 1.16–3.51, P = 0.007; AA vs. GG+GA: OR = 2.02, 95% CI = 1.15–3.33, P = 0.007; A vs. G: OR = 1.36, 95% CI = 1.07–1.81, P = 0.021). Additionally, the level of miR-34a was significantly up-regulated in IS patients compared to the controls ( P < 0.001), and patients with rs2666433 AA genotype had a higher level of miR-34a than those with GG+GA genotypes ( P < 0.001). Furthermore, increased level of homocysteine was observed in IS patients compared to the controls ( P < 0.001), especially in patients carrying the rs2666433AA genotype compared to those carrying the rs2666433 GG+GA genotypes ( P < 0.001). However, no significant association between rs12128240 or rs6577555 and IS was found. Collectively, our study found the association between miR-34a polymorphisms and the risk of IS among the Chinese population. The results may provide an explanation for etiology of IS and a potential biomarker or therapeutic target for IS. HIGHLIGHTS MiR-34a rs2666433 polymorphism was associated with an increased risk of ischemic stroke. The level of miR-34a was significantly up-regulated in ischemic stroke patients compared with controls, and patients with rs2666433 AA genotype had a higher level miR-34a than those with GG+GA genotypes. Furthermore, increased level of homocysteine was showed in IS patients compared to controls, and in patients carrying the rs2666433AA compared to those carrying the rs2666433 GG+GA.

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Section: Discussionmentioning

confidence: 99%

A Genetic Variant of miR-34a Contributes to Susceptibility of Ischemic Stroke Among Chinese Population

et al. 2019

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“…29 In 2012, Xia et al 27 performed a meta-analysis on 36 case-control studies and their results Few studies are available on the association of genetic polymorphisms at non-coding regions of MTHFR gene including 3′-untranslated region (3′-UTR) and various disease. [32][33][34] 3′-UTR region is a non-coding region of mRNA, could be the target of miRNAs. miRNAs are short noncoding RNAs that regulate gene expression at the posttranscriptional in eukaryote cells.…”

Section: Discussionmentioning

confidence: 99%

“…Few studies are available on the association of genetic polymorphisms at non‐coding regions of MTHFR gene including 3′‐untranslated region (3′‐UTR) and various disease . 3′‐UTR region is a non‐coding region of mRNA, could be the target of miRNAs.…”

Section: Discussionmentioning

confidence: 99%

Genetic variants in 3′‐UTRs of MTHFR in the pregnancies complicated with preeclampsia and bioinformatics analysis

Mohammadpour‐Gharehbagh

Salimi

Keshavarzi

et al. 2017

J of Cellular Biochemistry

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Preeclampsia (PE) as a pregnancy-specific disorder is the major cause of mortality and morbidity of mothers and fetuses. This study attempts to investigate the possible association between the 2572C>A (rs4846049) and 4869C>G (rs1537514) polymorphisms in the 3'- untranslated region of MTHFR gene and the risk of PE. A total of 198 patients diagnosed with PE and 171 unrelated, age matched healthy pregnant women, were recruited for this case-control study. The MTHFR 2572C>A and 4869C>G genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The CG genotype of MTHFR 4869C>G was associated with decreased risk of PE, and this genotype was found to be a protective factor for PE susceptibility. There was no significant difference in the genotypes of MTHFR 2572C>A polymorphism between PE patients and control group. The frequency of combined AC/CG genotypes of MTHFR 2572C>A and 4869C>G polymorphisms were less frequent in PE patients and were associated with a lower risk of PE. The C-G and A-G haplotypes of MTHFR 2572C>A and 4869C>G polymorphisms were significantly lower in PE patients. In conclusion, the CG genotype of MTHFR 4869C>G polymorphism was associated with a lower risk of PE. No association was found between MTHFR 2572C>A polymorphism and PE.

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“…The rs7646 polymorphism significantly affects miR-197 binding affinity to the MTHFD1L 3'UTR, causing more efficient post-transcriptional gene repression in the presence of the allele that is associated with increased risk of NTDs [40]. Similarly, there is a miR-34b binding site in the 3'UTR of the methylenetetrahydrofolate reductase (MTHFR) gene, which may be impacted by the rs55763075 polymorphism, which may alter 1CM and has been linked to risk for idiopathic azoospermia [41].…”

Section: Embryonic Developmentmentioning

confidence: 99%

Folate and microRNA: Bidirectional interactions

Beckett

Veysey

Lucock

2017

Clinica Chimica Acta

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Low folate status is linked to increased risk of a number of conditions, including developmental disorders, some cancers, neurodegenerative and cardiovascular diseases. Some of the mechanisms of these associations are known, but much remains to be elucidated. Aberrant microRNA (miRNA) profiles are also signatures of these conditions, and as such, the association between folate status and miRNA are now being investigated. Potential associations are bidirectional, with miRNA linked to regulation of folate-mediated pathways, and folate linked to modulation of miRNA expression. miRNA are short non-coding RNA, involved in post-transcriptional regulation of gene expression via complementary binding to mRNA. Evidence is emerging that links folate levels to the regulation of miRNA levels, and miRNA to the regulation of the expression of enzymes involved in folate mediated one carbon metabolism. One carbon metabolism is the source of methyl groups for methylation reactions, including DNA methylation and is important in DNA synthesis and repair. miRNA may be modulated by DNA methylation and other epigenetic mechanisms directly, or indirectly via modulation of upstream signalling pathways. As such, there may be bi-directional associations between folate status and miRNA profiles. miRNA may also act as biomarkers for diagnosis or prognosis of conditions associated with folate status.

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Association of a miR-34b binding site single nucleotide polymorphism in the 3'-untranslated region of the methylenetetrahydrofolate reductase gene with susceptibility to male infertility

Cited by 10 publications

References 40 publications

A Genetic Variant of miR-34a Contributes to Susceptibility of Ischemic Stroke Among Chinese Population

A Genetic Variant of miR-34a Contributes to Susceptibility of Ischemic Stroke Among Chinese Population

Genetic variants in 3′‐UTRs of MTHFR in the pregnancies complicated with preeclampsia and bioinformatics analysis

Folate and microRNA: Bidirectional interactions

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