Genetic variants in long noncoding RNA H19 and MEG3 confer risk of type 2 diabetes in an Iranian population

Ghaedi, Hamid; Zare, A Ghamari; Omrani, Mir Davood; Doustimotlagh, Amir Hossein; Meshkani, Reza; Alipoor, Sadegh; Alipoor, Behnam

doi:10.1016/j.gene.2018.07.002

Cited by 42 publications

(36 citation statements)

References 38 publications

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“…24 The correlation of rs3741219 and rs217727 polymorphisms and several cancers were confirmed in many studies. [24][25][26] Moreover, the effects of these polymorphisms and risk of diabetes, 27 coronary artery disease, 28 and ischemic stroke 29 were reported previously. Although the association of rs2107425 polymorphism which is located on the promoter region of H19 gene and risk of numerous diseases were reported in the previous studies, there is still no published study regarding the effect of this polymorphism on H19 expression.…”

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confidence: 66%

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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confidence: 66%

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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“…Gao et al (2014) reported that rs217727 polymorphism in the H19 gene was correlated with an increased risk of coronary artery disease [20]. Moreover, Ghaedi et al demonstrated an association between H19 rs217727 polymorphism with type 2 diabetes susceptibility [21]. Coronary artery disease and diabetes are two main risk factors for IS [22,23].…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies suggested that rs217727 polymorphism is related to the pathogenesis of breast cancer, oral squamous cell carcinoma, and type 2 diabetes susceptibility in the Iranian population [21,26,27]. Research on the role of lncRNAs in IS pathogenesis is just beginning, and we have performed this study to assess the association between lncRNA H19 expression and its rs217727 polymorphism with susceptibility to IS in the Iranian population.…”

Section: Introductionmentioning

confidence: 99%

Long Non-Coding RNA H19 Expression and Functional Polymorphism rs217727 Are Linked to Increased Ischemic Stroke Risk

Rezaei

Mokhtari

Bayat

et al. 2020

Preprint

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Background: Efforts to identify potential biomarkers for the diagnosis of ischemic stroke (IS) are valuable. The H19 gene plays a functional role in increasing the prevalence of IS risk factors. We evaluated the correlation between H19 rs217727 polymorphism and the expression level of H19 lncRNA with susceptibility to IS among the Iranian population.Methods: Blood samples were collected from IS patients (n = 114) and controls (n = 114). We concentrated on the expression pattern of H19 at different time points (i.e., 0-24, 24-48, and 48-72 hours after stroke). The tetra-primer ARMS-PCR method was applied for DNA genotyping. We used the quantitative real-time PCR to evaluate H19 expression levels. Results: The rs217727polymorphism of H19 was related with IS susceptibility in the co-dominant (OR=2.92, 95% CI=0.91-10.92, P=0.04) and recessive models (OR=2.80, 95% CI=0.96-8.15, P=0.04). H19 expression was signiﬁcantly upregulated in IS and remained high for 72 hours after stroke. ROC curves showed that H19 expression within the first 24 hours from stroke onset might serve as a biomarker for the early diagnosis of IS with 79.49% sensitivity and 80.00% specificity. H19 expression in SVO and LAA patients were 3.74 and 3.34 times higher than the UD subtype, respectively [OR=3.74 95% CL (1.14-12.27) P=0.030 and OR=3.34 95% CL (1.13-9.85) P=0.029].Conclusion: The rs217727 polymorphism of the H19 is correlated with IS susceptibility, and H19 expression levels were higher in SVO and LAA patients. The upregulation of H19 may be considered as a diagnostic biomarker in IS among the Iranian population.

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“…The H19 rs217727 and rs3741219 single nucleotide polymorphism (SNP) loci and the MEG3 rs7158663 SNP locus are located at the miRNA-binding sites of these lncRNAs (Ghaedi et al, 2018). We speculated that the SNPs might affect the binding efficiency of the lncRNAs to miR-NAs and, in turn, alter the regulation of the miRNAs by the lncRNAs.…”

Section: Introductionmentioning

confidence: 99%

“…Although there is no evidence to support that the rs3741219 locus is associated with the risk of OA, similar to the rs217727 locus, the rs3741219 locus is also located at the binding site of lncRNA H19 and miRNA, and the role of its genetic variation on the function of lncRNA H19 is not clear. Ghaedi et al (2018) showed that there is a significant correlation between MEG3 rs7158663-AA genotype and type 2 diabetes susceptibility. Therefore, we selected these SNP sites and designed a case-control study to analyze the H19 gene rs217727 and rs3741219 loci SNPs and the MEG3 gene rs7158663 locus SNP in 230 patients with OA and 230 control individuals, as well as their associations with the risk of OA.…”

Section: Introductionmentioning

confidence: 99%

Association of Long-Chain Noncoding RNA H19 and MEG3 Gene Polymorphisms and Their Interaction with Risk of Osteoarthritis in a Chinese Han Population

Wang

Cheng

et al. 2020

Genetic Testing and Molecular Biomarkers

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Objective: To analyze the association of single nucleotide polymorphisms (SNPs) in the long-chain noncoding RNAs (lncRNAs) H19 and maternal expressed gene 3 (MEG3) with the risk of osteoarthritis (OA) in a Chinese Han population. Methods: A total of 230 patients with OA and 230 control subjects were recruited. Sanger sequencing was used to analyze the genotypes of the H19 gene rs217727 and rs3741219 loci and the MEG3 gene rs7158663 locus. Quantitative real-time reverse transcription-polymerase chain reaction was used to determine the levels of the microRNAs (miRNA) hsa-miR-4804-5p, hsa-miR-8071, hsa-miR-8072, hsa-miR-3960, hsa-miR-4307, and hsa-miR-1265 in the plasma. Results: The risk of OA was significantly increased by the A allele of the rs217727 locus of H19 (odds ratio = 1.27, 95% confidence interval [CI]: 1.09-1.42, p = 0.001). The H19 gene rs3741219 locus SNP had no significant correlation with the risk of OA (p > 0.05). The risk of OA in subjects carrying the rs7158663 locus A allele of MEG3 was 1.32 times higher compared with those carrying the G allele (95% CI: 1.16-1.50, p < 0.01). SNP rs217727 of H19 was associated with the plasma levels of lncRNA H19, hsa-miR-4804-5p, hsa-miR-8071, hsa-miR-8072, and hsa-miR-3960, and SNP rs7158663 in MEG3 was associated with the plasma levels of lncRNA MEG3, hsa-miR-4307, and hsa-miR-1265. Conclusion: Specific SNPs of the H19 rs217727 and MEG3 rs7158663 loci are associated with the risk of OA. The possible underlying molecular mechanisms, which remain to be confirmed, are their likely influence on the expression levels of the lncRNA H19 and MEG3, which in turn alters the expression level of their target miRNAs.

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Genetic variants in long noncoding RNA H19 and MEG3 confer risk of type 2 diabetes in an Iranian population

Cited by 42 publications

References 38 publications

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

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

Long Non-Coding RNA H19 Expression and Functional Polymorphism rs217727 Are Linked to Increased Ischemic Stroke Risk

Association of Long-Chain Noncoding RNA H19 and MEG3 Gene Polymorphisms and Their Interaction with Risk of Osteoarthritis in a Chinese Han Population

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