The association of the placental MTHFR 3′‐UTR polymorphisms, promoter methylation, and MTHFR expression with preeclampsia

Mohammadpour‐Gharehbagh, Abbas; Teimoori, Batool; Narooei‐Nejad, Mehrnaz; Mehrabani, Mehrnaz; Saravani, Ramin; Salimi, Saeedeh

doi:10.1002/jcb.26290

Cited by 20 publications

(12 citation statements)

References 37 publications

(93 reference statements)

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“…The inconsistent results may be caused by different races and different sample size, which was larger in our study. Previously, some studies also reported the correlation between rs4846049 and others diseases, including migraine,[ 18 ] colorectal cancer,[ 19 ] preeclampsia,[ 20 ] and coronary heart disease. [ 21 22 ] Yu et al .…”

Section: Discussionmentioning

confidence: 99%

Interaction between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and environment with susceptibility to ischemic stroke in Chinese population

Zheng¹,

Bian²,

Sun³

et al. 2020

Ann Indian Acad Neurol

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Aims: To investigate the association of several single-nucleotide polymorphisms (SNPs) within methylenetetrahydrofolate reductase (MTHFR) gene, and additional gene–environment interaction with ischemic stroke (IS) risk. Methods: Testing for Hardy–Weinberg equilibrium in controls was conducted using SNPstats (online software: http://bioinfo.iconcologia.net/SNPstats ). Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among four SNPs within MTHFR gene and smoking or alcohol drinking. Results: The frequency of the rs4846049-A allele was 28.6% in IS patients and 19.1% in normal controls, in addition, the frequency of the rs3737967-T allele was 27.9% in IS patients and 20.3% in normal controls, which was also indicating a statistically significant difference. The rs4846049-A and rs3737967-T were associated with an increased risk of IS risk; adjusted odds ratios (ORs) (95% confidence interval [CI]) were 1.76 (1.28–2.13) and 1.51 (1.13–1.97), respectively. GMDR model found significant gene–alcohol drinking interaction combination, but no significant gene–tobacco smoking interaction combinations. In order to obtain the odds ratios and 95% CI for the joint effects of gene–alcohol drinking on IS, we conducted stratified analysis for interaction effect using logistic regression. We found that alcohol drinkers with rs4846049-CA/AA genotype also have the highest IS risk, compared with never drinkers with rs4846049-CC genotype, OR (95% CI) = 3.12 (1.83–4.45), after adjustment for age, smoke, and smoking status. Conclusions: The rs4846049-A and rs3737967-T, gene–environment interaction between rs1764391 and rs918592, gene–environment interaction between rs4846049 and alcohol drinking were all associated with increased IS risk.

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Section: Discussionmentioning

confidence: 99%

Interaction between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and environment with susceptibility to ischemic stroke in Chinese population

Zheng¹,

Bian²,

Sun³

et al. 2020

Ann Indian Acad Neurol

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“…There are also several studies which have provided evidence that the PE pathogenesis is correlated with the promoter methylation status of relevant genes . Based on the effect of promoter region DNA methylation on regulating the expression of genes related to invasiveness of trophoblasts, the importance of promoter methylaytion in gene expression during normal pregnancy and potential of their deregulation in the development of PE have been reported previously …”

Section: Discussionmentioning

confidence: 99%

The effects of placental long noncoding RNA H19 polymorphisms and promoter methylation on H19 expression in association with preeclampsia susceptibility

et al. 2019

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The effect of DNA methylation on gene expression triggered it as a susceptibility factor in various diseases including preeclampsia (PE). The pathogenesis of PE is closely associated with the methylation status and genetic variants of relevant genes. Therefore, the aim of the study was to investigate the possible impacts of the placental DNA methylation and rs3741219, rs217727, and rs2107425 polymorphisms of the H19 gene on the PE susceptibility as well as the its mRNA expression. Moreover, eight haplotypes of three loci in the H19 gene were analyzed. In this case‐control study, the placentas of 107 preeclamptic and 113 non‐preeclamptic women were collected after delivery. The methylation status was assessed by methylation‐specific polymerase chain reaction (PCR). The H19 polymorphisms were genotyped using polymerase chain reaction‐restriction fragment length polymorphism or amplification refractory mutation system‐polymerase chain reaction methods. The quantitative real time PCR was used for mRNA expression assay. The placental H19 rs3741219 and rs2107425 polymorphisms were not associated with PE. However, H19 rs217727CT and TT genotypes might be associated with a 9.2‐ and 17.7‐fold increased risk of PE, respectively. The Trs3741219 Crs217727 Crs2107425 and Trs3741219 Crs217727 Trs2107425 haplotypes were significantly lower, whereas the Trs3741219 Trs217727 Crs2107425 and Crs3741219 Trs217727 Crs2107425 haplotypes were significantly higher in PE women. Promoter but not upstream region hypermethylation of H19 gene could be led to decreased risk of PE (MM vs. UM + UU). No significant difference was observed in the placental mRNA expression between two groups. The H19 expression was significantly higher in women with unmethylated (UU), compared to methylated promoter (MM). The H19 expression was 17‐ and 15‐fold higher in H19‐rs2107425 CC and CT genotypes in PE women. In conclusion, the H19 rs2107425 polymorphism was associated with a higher risk of PE and increased H19 mRNA expression. The promoter hypermethylation of H19 gene was associated with a lower risk of PE and decreased H19 mRNA expression.

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“…Previously, there have studies to explore the association of MTHFR rs4846049 polymorphism and susceptibility to migraine [20], ischemic stroke [21], preeclampsia [22, 23], colorectal cancer [18], coronary artery disease [24, 25], attention-deficit/hyperactivity disorder [26], and cerebral palsy [27]. In the study of Salehi et al [20], T allele (OR = 0.72, 95% CI = 0.56–0.93; P =0.01) and genotype of GT (OR = 0.61, 95% CI = 0.41–0.91; P =0.01), TT (OR = 0.57, 95% CI = 0.34–0.94; P =0.02), and GT + TT (OR = 0.60, 95% CI = 0.41–0.87; P =0.007) were suggested to be protective risk factors for migraine.…”

Section: Discussionmentioning

confidence: 99%

“…In the study of Salehi et al [20], T allele (OR = 0.72, 95% CI = 0.56–0.93; P =0.01) and genotype of GT (OR = 0.61, 95% CI = 0.41–0.91; P =0.01), TT (OR = 0.57, 95% CI = 0.34–0.94; P =0.02), and GT + TT (OR = 0.60, 95% CI = 0.41–0.87; P =0.007) were suggested to be protective risk factors for migraine. Although no significant differences between preeclampsia and controls were observed, the ORs of TT and GT genotype were shown to be less than 1 and the expression of MTHFR was found to be relatively lower in patients with GG and GT genotype compared with TT [22], which indirectly explain the risk factor of G allele. Also, accumulating evidence has proved the MTHFR enzyme expression and activity were reduced and plasma homocysteine level was increased in patients with preeclampsia compared with normotensive pregnancy [28, 29].…”

Section: Discussionmentioning

confidence: 99%

Rs4846049 Polymorphism at the 3′-UTR of MTHFR Gene: Association with Susceptibility to Childhood Acute Lymphoblastic Leukemia

Zhang

2019

BioMed Research International

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Background Accumulating evidence has suggested the polymorphisms of methylenetetrahydrofolate reductase (MTHFR) were associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). However, the known conclusions of currently known polymorphic loci (677 C > T and 1298 A > C) remain controversial. This study was to investigate new genetic biomarkers for ALL by analyzing the MTHFR polymorphisms at the 3′-untranslated region, which is a location bound by miRNAs. Methods Polymorphisms of rs4846049 (miR-555 binding) were assessed by PCR amplification and direct sequencing in 110 ALL patients and 105 healthy controls. The relative expression of MTHFR was detected by qRT-PCR. Results Overall, genotype distribution or allele carrier frequencies were not significantly different between patients with ALL and healthy controls (P > 0.05). Subgroup analysis results showed that T allele (OR = 0.134, 95% CI = 0.028–0.639; P=0.005) or genotypes with T allele (TT + GT) (OR = 0.133, 95% CI: 0.024–0.727; P=0.017) may be a protective factor for ALL susceptibility in patients with age >8 years. This conclusion was also true for the group only focusing on the precursor B-cell ALL patients. Furthermore, karyotype abnormality was more commonly observed in patients with the GG genotype (56.0%) compared to carriers of TT (0%) or GT (40.6%) genotypes, while c-myc break frequency was significantly higher in TT carriers (33%) than that of patients with GT (3.1%) or GG (0%) genotypes. PCR analysis showed patients carrying the GG genotype of rs4846049 exhibited the reduced mRNA expression of MTHFR. Conclusion MTHFR rs4846049 polymorphism may be associated with increased risk of childhood with ALL and MTHFR mRNA expression.

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The association of the placental MTHFR 3′‐UTR polymorphisms, promoter methylation, and MTHFR expression with preeclampsia

Cited by 20 publications

References 37 publications

Interaction between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and environment with susceptibility to ischemic stroke in Chinese population

Interaction between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and environment with susceptibility to ischemic stroke in Chinese population

The effects of placental long noncoding RNA H19 polymorphisms and promoter methylation on H19 expression in association with preeclampsia susceptibility

Rs4846049 Polymorphism at the 3′-UTR of MTHFR Gene: Association with Susceptibility to Childhood Acute Lymphoblastic Leukemia

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