A common indel polymorphism of the Desmoglein-2 (DSG2) is associated with sudden cardiac death in Chinese populations

Zou, Yan; Zhang, Qing; Zhang, Jianhua; Chen, Xue-Kun; Zhou, Wei; Yang, Zhenzhen; Yang, Qi; Yu, Huan; Li, Lijuan; Li, Chengtao; Zhang, Suhua; Zhu, Shijia; Luo, Baoming; Gao, Yuzhen

doi:10.1016/j.forsciint.2019.06.008

Cited by 13 publications

(7 citation statements)

References 32 publications

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“…[85], NOTCH2 [86], LRP1 [87], CLU (clusterin) [88], FCN1 [89], CDKN1A [90], SMAD3 [91], HLA-E [92], PTPRC (protein tyrosine phosphatase receptor type C) [93], MYH9 [94], JAK3 [95], IL6R [96], TIMP1 [97], DOCK8 [98], TNFRSF1B [99], ITGAL (integrin subunit alpha L) [100], CD47 [101], RARA (retinoic acid receptor alpha) [102], DGKD (diacylglycerol kinase delta) [103], PLEK (pleckstrin) [104], PREX1 [105], BSCL2 [106], PANX1 [107], IRF7 [108] [116] were revealed to be expressed in diabetes mellitus, but these genes might be novel targets for GDM. SIX1 [117], GREM1 [118], GHRHR (growth hormone releasing hormone receptor) [119], GPR37L1 [120], CYP2J2 [121], AQP4 [122], ROS1 [123], LBP (lipopolysaccharide binding protein) [124], SGCD (sarcoglycan delta) [133], PTHLH [134], FAP (fibroblast activation protein alpha) [135], THSD7A [136], SHROOM3 [137], ETV1 [138], CYP24A1 [139], SLIT2 [140], GJC1 [141], PPARGC1A [142], TRPM3 [143], IGF1 [144], TRPV6 [145], TLR3 [146], BMP7 [147], DSG2 [148], POSTN (periostin) [149], ENOX1 [150], KCNA7…”

Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed genes and signaling pathways in gestational diabetes mellitus by integrated bioinformatics analysis

Vastrad¹,

Vastrad²

2021

Preprint

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Gestational diabetes mellitus (GDM) is a metabolic disorder during pregnancy. Numerous biomarkers have been identified that are linked with the occurrence and development of GDM. The aim of this investigation was to identify differentially expressed genes (DEGs) in GDM using a bioinformatics approach to elucidate their molecular pathogenesis. GDM associated expression profiling by high throughput sequencing dataset (GSE154377) was obtained from Gene Expression Omnibus (GEO) database including 28 normal pregnancy samples and 33 GDM samples. DEGs were identified using DESeq2. The gene ontology (GO) and REACTOME pathway enrichments of DEGs were performed by g:Profiler. Protein-protein interaction (PPI) networks were assembled with Cytoscape software and separated into modules using the PEWCC1 algorithm. MiRNA-hub gene regulatory network and TF-hub gene regulatory network were performed with the miRNet database and NetworkAnalyst database. Receiver Operating Characteristic (ROC) analyses was conducted to validate the hub genes. A total of 953 DEGs were identified, of which 478 DEGs were up regulated and 475 DEGs were down regulated. Furthermore, GO and REACTOME pathway enrichment analysis demonstrated that these DEGs were mainly enriched in multicellular organismal process, cell activation, formation of the cornified envelope and hemostasis. TRIM54, ELAVL2, PTN, KIT, BMPR1B, APP, SRC, ITGA4, RPA1 and ACTB were identified as key genes in the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network. TRIM54, ELAVL2, PTN, KIT, BMPR1B, APP, SRC, ITGA4, RPA1 and ACTB in GDM were validated using ROC analysis. This investigation provides further insights into the molecular pathogenesis of GDM, which might facilitate the diagnosis and treatment of GDM.

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Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed genes and signaling pathways in gestational diabetes mellitus by integrated bioinformatics analysis

Vastrad¹,

Vastrad²

2021

Preprint

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“…The samples of SCD victims were collected from the following institutions during autopsy cases for medicolegal purpose: Soochow University and Institute of Forensic Sciences (China Ministry of Justice) representing Eastern China (20 cases), Sun Yat-sen University representing Southern China (103 cases) and Guizhou Medical University representing Southwestern China (35 cases). The blood samples were collected for the current study following the inclusive and exclusive criteria described previously ( Wang et al, 2017 ; Zou et al, 2019 ). In brief, detailed forensic pathological examination was rigorously performed with each SCD case to confirm the coronary heart diseases as the main cause of SCD.…”

Section: Methodsmentioning

confidence: 99%

Novel Indel Variation of NPC1 Gene Associates With Risk of Sudden Cardiac Death

et al. 2022

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Background and Aims: Sudden cardiac death (SCD) was defined as an unexpected death from cardiac causes during a very short duration. It has been reported that Niemann-Pick type C1 (NPC1) gene mutations might be related to cardiovascular diseases. The purpose of the study is to investigate whether common genetic variants of NPC1 is involved in SCD susceptibility.Methods: Based on a candidate-gene-based approach and systematic screening strategy, this study analyzed an 8-bp insertion/deletion polymorphism (rs150703258) within downstream of NPC1 for the association with SCD risk in Chinese populations using 158 SCD cases and 524 controls. The association of rs150703258 and SCD susceptibility was analyzed using logistic regression. Genotype-phenotype correlation analysis was performed using public database including 1000G, expression quantitative trait loci (eQTL), and further validated by human heart tissues using PCR. Dual-luciferase assay was used to explore the potential regulatory role of rs150703258. Gene expression profiling interactive analysis and transcription factors prediction were performed.Results: Logistic regression analysis exhibited that the deletion allele of rs150703258 significantly increased the risk of SCD [odds ratio (OR) = 1.329; 95% confidence interval (95%CI):1.03–1.72; p = 0.0289]. Genotype-phenotype correlation analysis showed that the risk allele was significantly associated with higher expression of NPC1 at mRNA and protein expressions level in human heart tissues. eQTL analysis showed NPC1 and C18orf8 (an adjacent gene to NPC1) are both related to rs150703258 and have higher expression level in the samples with deletion allele. Dual-luciferase activity assays indicate a significant regulatory role for rs150703258. Gene expression profiling interactive analysis revealed that NPC1 and C18orf8 seemed to be co-regulated in human blood, arteries and heart tissues. In silico analysis showed that the rs150703258 deletion variant may create transcription factor binding sites. In addition, a rare 12-bp allele (4-bp longer than the insertion allele) of rs150703258 was discovered in the current cohort.Conclusion: In summary, our study revealed that rs150703258 might contribute to SCD susceptibility by regulating NPC1 and C18orf8 expression. This indel may be a potential marker for risk stratification and molecular diagnosis of SCD. Validations in different ethnic groups with larger sample size and mechanism explorations are warranted to confirm our findings.

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“…The SCD blood samples were obtained from the following institutions during 2012-2019: Soochow University, Institute of Forensic Science, Ministry of Justice, and Sun Yat-sen University. The criterion of sample selection for the current study follows the principles described previously (22,23). Briefly, all SCD cases caused by coronary heart diseases or hypertrophic cardiomyopathy were confirmed by rigorous forensic pathological investigation.…”

Section: Study Populationsmentioning

confidence: 99%

A Functional Indel Polymorphism Within MIR155HG Is Associated With Sudden Cardiac Death Risk in a Chinese Population

Zhang

Yang

et al. 2021

Front. Cardiovasc. Med.

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Sudden cardiac death (SCD) is a devastating complication of multiple disease processes and has gradually became a major public health issue. miR-155 is one of the best characterized miRNAs and plays a critical role in several physiological and pathological process, including cardiovascular diseases. In this study, we systematically screened the whole region of miR-155 host gene (MIR155HG) and identified a 4-bp insertion/deletion variant (rs72014506) residing in the intron region of MIR155HG as the candidate polymorphism. The association of rs72014506 with SCD susceptibility was evaluated using 166 SCD cases and 830 healthy controls in a Chinese population. Logistic regression analysis suggested that the homozygote del/del genotype significantly decreased the risk of SCD [odds ratio (OR) = 0.29; 95% confidence interval (CI) = 0.12–0.74; Ptrend = 0.0004]. Further genotype–expression association study using human myocardium tissue samples suggested that the deletion allele was intimately linked to lower the expression of both MIR155HG and mature miR155. Luciferase activity assay also revealed that the deletion allele of rs72014506 inhibited gene transcriptional activity. Finally, we performed electrophoretic mobility shift assay and verified the preferential binding affinity of the deletion allele with POU2F1 (POU domain class 2 transcription factor 1). Collectively, we have successfully identified a SCD risk conferring polymorphism in the MIR155HG gene and a likely biological mechanism for the decreased risk of SCD associated with the deletion allele. This novel variant may thus serve as a potential genetic marker for SCD diagnosis and prevention in natural populations, if validated by further studies with a larger sample size.

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A common indel polymorphism of the Desmoglein-2 (DSG2) is associated with sudden cardiac death in Chinese populations

Cited by 13 publications

References 32 publications

Identification of differentially expressed genes and signaling pathways in gestational diabetes mellitus by integrated bioinformatics analysis

Identification of differentially expressed genes and signaling pathways in gestational diabetes mellitus by integrated bioinformatics analysis

Novel Indel Variation of NPC1 Gene Associates With Risk of Sudden Cardiac Death

A Functional Indel Polymorphism Within MIR155HG Is Associated With Sudden Cardiac Death Risk in a Chinese Population

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