Association between single nucleotide polymorphisms in MiR219‐1 and MiR137 and susceptibility to schizophrenia in a Chinese population

Sun, Yunyan; Yu, Ying; Zhu, Gao-Ceng; Sun, Zhu-Hua; Xu, Jian; Cao, Jianhua; Ge, Jianxin

doi:10.1016/j.fob.2015.08.008

Cited by 14 publications

(9 citation statements)

References 42 publications

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“…Since our previous findings demonstrated that miR-219a over expression severely increases Scn5a expression [11], so we hypothesized that rs107822 within pri-miR-219a would affect its structure or expression, leading to an impaired miR-219a expression (most likely decreasing) which in turn will lead to a decreased SCN5A expression. Recently, Song et al demonstrated that the miR-219a rs107822 GA and AA genotypes decreased the mature miR-219a expression compared with the miR-219a rs107822 GG genotypes in normal tissues which further supports our hypothesis [34] Although the functionality of this polymorphism has been studied in several pathological contexts including cancers and psychological disorders [35,36], to our knowledge, it's the first time that the rs107822 is identified in patients with cardiac diseases particularly BrS.…”

Section: Discussionsupporting

confidence: 79%

Role of SCN5A coding and non-coding sequences in Brugada syndrome onset: What’s behind the scenes?

Daimi

Khelil

Neji

et al. 2017

Preprint

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Brugada syndrome (BrS) is a rare inherited cardiac arrhythmia associated with a high risk of sudden cardiac death (SCD) due to ventricular fibrillation (VF). BrS is characterized by coved-type ST-segment elevation in the right precordial leads (V1-V3) in the absence of structural heart disease. This pattern is spontaneous, or is unmasked by intravenous administration of Class I antiarrhythmic drugs. The SCN5A-encoded α -subunit of the NaV1.5 cardiac sodium channel has been linked to BrS, and mutations in SCN5A are identified in 15-30% of BrS cases. Genetic testing of BrS patients generally involves sequencing of protein-coding portions and flanking intronic regions of SCN5A, according to recent international guidelines. This excludes the regulatory untranslated regions (5'UTR and 3'UTR) from the routine genetic testing of BrS patients. We here screened the coding sequence, the flanking intronic regions as well as the 5' and 3'UTR regions of SCN5A gene and further five candidate genes (GPD1L, SCN1B, KCNE3, SCN4B, and MOG1) in a Tunisian family diagnosed with Brugada syndrome.A new Q1000K mutation was identified on the SCN5A gene along with two common polymorphisms (H558R and D1819). Furthermore, multiple genetic variants were identified on the SCN5A 3´UTR, one of which is predicted to create additional microRNA (miRNAs) binding site for miR-1270. Additionally, we identified the hsa-miR-219a rs107822. No relevant coding sequence variant was identified in the remaining studied candidate genes.Although Q1000K is localized in the conserved binding site of MOG1 which predicts a functional consequence, this new mutation along with the additional variants were differentially distributed among the family members without any clear genotype-phenotype concordance. This gives extra evidences about the complexity of the disease and suggests that the occurrence and prognosis of BrS is most likely controlled by a combination of multiple genetic factors and exposures, rather than a single polymorphism/mutation. Most SCN5A polymorphisms were localized in non-coding regions hypothesizing an impact on the miRNA-target complementarities. In this regard, over-

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Section: Discussionsupporting

confidence: 79%

Role of SCN5A coding and non-coding sequences in Brugada syndrome onset: What’s behind the scenes?

Daimi

Khelil

Neji

et al. 2017

Preprint

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“…A similar analysis carried out in patients with schizophrenia from Singapore has demonstrated a significant increase ( p = 0.016) in negative symptomatology in T/T patients compared to the subjects with G/G or G/T genotypes ( 8 ). Data obtained by three independent Chinese investigation groups showed no association of the studied locus with scores for PANSS subscales ( 14 , 16 , 25 ). Possibly, these controversial results may be explained by ethnical heterogeneity as well as the limited sample sizes.…”

Section: Discussionmentioning

confidence: 81%

Association of MIR137 With Symptom Severity and Cognitive Functioning in Belarusian Schizophrenia Patients

et al. 2018

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MicroRNA-137 (miRNA-137; miR-137) is one of the important post-transcriptional regulators of the nervous system development, and its MIR137 gene rs1625579 polymorphism was reported to be a potential regulator for schizophrenia susceptibility. However, schizophrenia characteristics controlled by MIR137 rs1625579 polymorphism are still insufficiently understood. There were 3 groups included in the study: (a) subjects with diagnosis of schizophrenia (n = 150; 81-females, 69-males), (b) mentally healthy people (control group; n = 102; 66-females, 36-males) and (c) Belarusian indigenous male group (n = 295). Associations of rs1625579 with schizophrenia, symptom's severity and cognitive performance [by using Positive and Negative Syndrome Scale (PANSS) and Wisconsin Card Sorting Test (WCST), respectively] were studied, when compared to controls. Allele and genotype frequencies were investigated in Belarusian indigenous males. Rs1625579 displayed no association with schizophrenia in Belarusian population. Significant “symptom severity-genotype” interactions were revealed for schizophrenia patients. Patients with T/G genotype displayed lower severity of positive symptoms and general psychopathology compared to homozygous subjects. T/T genotype was associated with the highest symptom's severity. The negative symptom scores and the total PANSS-score were significantly higher in females carrying genotype T/T vs. T/G+G/G; no significant gene-phenotype associations were found in males. WCST parameters did not show any association with rs1625579 polymorphism. MIR137 rs1625579 polymorphism might be an important sex-dependent factor influencing severity of schizophrenia psychopathological manifestations. These findings also contribute to the knowledge on candidate gene effects on characteristics related to schizophrenia phenotype. As miR 137 is considered to be cancer therapeutic target, miR-137 may also explain the lower incidence of cancer in schizophrenia patients. Further studies with larger sample size are needed to confirm these novel findings.

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“…A number of studies have reported an association between the SNPs in the MIR137 gene and the incidence of schizophrenia, with the T allele at the MIR137 SNP rs1625579 being most consistently associated with an increased risk of schizophrenia [ 56 , 57 , 58 , 59 ]. By contrast, some other studies have failed to show an association of any MIR137 SNPs and schizophrenia [ 60 , 61 , 62 ]. However, a meta-analysis of 12 case-control studies showed an association between rs1625579 and the incidence of schizophrenia, reporting that the T allele is associated with a 15% increase in the risk of developing schizophrenia compared to the G allele and that patients with the T/T genotype were at a 32% greater risk developing schizophrenia compared to those with the G/G genotype [ 63 ].…”

Section: Mir-137 In Schizophreniamentioning

confidence: 87%

Non-Coding RNA as Novel Players in the Pathophysiology of Schizophrenia

Gibbons

Udawela

Dean

2018

ncRNA

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Schizophrenia is associated with diverse changes in the brain’s transcriptome and proteome. Underlying these changes is the complex dysregulation of gene expression and protein production that varies both spatially across brain regions and temporally with the progression of the illness. The growing body of literature showing changes in non-coding RNA in individuals with schizophrenia offers new insights into the mechanisms causing this dysregulation. A large number of studies have reported that the expression of microRNA (miRNA) is altered in the brains of individuals with schizophrenia. This evidence is complemented by findings that single nucleotide polymorphisms (SNPs) in miRNA host gene sequences can confer an increased risk of developing the disorder. Additionally, recent evidence suggests the expression of other non-coding RNAs, such as small nucleolar RNA and long non-coding RNA, may also be affected in schizophrenia. Understanding how these changes in non-coding RNAs contribute to the development and progression of schizophrenia offers potential avenues for the better treatment and diagnosis of the disorder. This review will focus on the evidence supporting the involvement of non-coding RNA in schizophrenia and its therapeutic potential.

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Association between single nucleotide polymorphisms in MiR219‐1 and MiR137 and susceptibility to schizophrenia in a Chinese population

Abstract: HighlightsA case-control study investigated rs107822, rs1625579 and risk of schizophrenia.rs107822 was negatively associated with susceptibility to schizophrenia.No association was found between rs1625579 and the disorder.

Cited by 14 publications

References 42 publications

Role of SCN5A coding and non-coding sequences in Brugada syndrome onset: What’s behind the scenes?

Role of SCN5A coding and non-coding sequences in Brugada syndrome onset: What’s behind the scenes?

Association of MIR137 With Symptom Severity and Cognitive Functioning in Belarusian Schizophrenia Patients

Non-Coding RNA as Novel Players in the Pathophysiology of Schizophrenia

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