Association of caspase-1 polymorphisms with Chagas cardiomyopathy among individuals in Santa Cruz, Bolivia

Fu, Katherine Y.; Zamudio, Roxana; Henderson-Frost, Jo; Almuedo, Alex; Steinberg, Hannah; Clipman, Steven J.; Duran, Gustavo; Marcus, Rachel; Crawford, Thomas; Alyesh, Daniel; Colanzi, Rony; Flores, Jorge; Gilman, Robert H.; Bern, Caryn

doi:10.1590/0037-8682-0015-2017

Cited by 6 publications

(4 citation statements)

References 37 publications

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“…In contrast with this data, Blankenberg et al reported that in Caucasian patients with CAD, the A allele of the rs501192 A / G polymorphism exhibited a borderline association with a decreased risk of developing CAD ( p = 0.053) [ 22 ]. Alternatively, prior studies have shown (with positive and negative results in different populations) that the rs580253 A / G and rs501192 A / G polymorphisms have an important role in the development of diseases such as ACS, Chagas cardiomyopathy, Alzheimer’s, and cancer [ 15 , 23 , 24 , 25 ]. On the other hand, our results showed an increased frequency of the haplotypes ( AG and GA ) conformed by rs580253 A / G and rs501192 A / G polymorphisms in patients with restenosis.…”

Section: Discussionmentioning

confidence: 99%

CASP1 Gene Polymorphisms and BAT1-NFKBIL-LTA-CASP1 Gene–Gene Interactions Are Associated with Restenosis after Coronary Stenting

et al. 2022

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In the present study, we evaluated the association of the BAT1, NFKBIL, LTA, and CASP1 single nucleotide polymorphisms and the gene–gene interactions with risk of developing restenosis after coronary stenting. The allele and genotype determination of the polymorphisms (BAT1 rs2239527 C/G, NFKBIL1 rs2071592 T/A, LTA rs1800683 G/A, CASP1 rs501192 A/G, and CASP1 rs580253 A/G) were performed by 5’exonuclease TaqMan assays in 219 patients: 66 patients with restenosis and 153 without restenosis. The distribution of rs2239527 C/G, rs2071592 T/A, and rs1800683 G/A polymorphisms was similar in patients with and without restenosis. Nonetheless, under recessive (OR = 2.73, pCRes = 0.031) and additive models (OR = 1.65, pCAdd = 0.039), the AA genotype of the rs501192 A/G polymorphism increased the restenosis risk. Under co-dominant, dominant, recessive, and additive models, the AA genotype of the rs580253 A/G was associated with a high restenosis risk (OR = 5.38, pCCo-Dom = 0.003; OR = 2.12, pCDom = 0.031; OR = 4.32, pCRes = 0.001; and OR = 2.16, 95%CI: 1.33–3.52, pCAdd = 0.001, respectively). In addition, we identified an interaction associated with restenosis susceptibility: BAT1-NFKBIL1-LTA-CASP1 (OR = 9.92, p < 0.001). In summary, our findings demonstrate that the rs501192 A/G and rs580253 A/G polymorphisms, as well as the gene–gene interactions between BAT1-NFKBIL1-LTA-CASP1, are associated with an increased restenosis risk after coronary stenting.

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Section: Discussionmentioning

confidence: 99%

CASP1 Gene Polymorphisms and BAT1-NFKBIL-LTA-CASP1 Gene–Gene Interactions Are Associated with Restenosis after Coronary Stenting

et al. 2022

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“…In a mouse model, overexpression of LPAR2 induces intestinal dysplasia, which therefore alters the proliferation and differentiation of the intestinal epithelial cells (IEC) [ 78 ]. The pivotal inflammasome component, Caspase-1 , is an emerging player in various diseases progressions, as well as a biomarker for early diagnosis and a therapeutic target [ 79 , 80 , 81 , 82 ]. The encoded protein of the NHS gene regulates the development of brain, craniofacial, eye, and tooth, in addition to actin remodeling and thus maintaining cell morphology.…”

Section: Discussionmentioning

confidence: 99%

Identification of Differentially Methylated CpG Sites in Fibroblasts from Keloid Scars

et al. 2020

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As a part of an abnormal healing process of dermal injuries and irritation, keloid scars arise on the skin as benign fibroproliferative tumors. Although the etiology of keloid scarring remains unsettled, considerable recent evidence suggested that keloidogenesis may be driven by epigenetic changes, particularly, DNA methylation. Therefore, genome-wide scanning of methylated cytosine-phosphoguanine (CpG) sites in extracted DNA from 12 keloid scar fibroblasts (KF) and 12 control skin fibroblasts (CF) (six normal skin fibroblasts and six normotrophic fibroblasts) was conducted using the Illumina Human Methylation 450K BeadChip in two replicates for each sample. Comparing KF and CF used a Linear Models for Microarray Data (Limma) model revealed 100,000 differentially methylated (DM) CpG sites, 20,695 of which were found to be hypomethylated and 79,305 were hypermethylated. The top DM CpG sites were associated with TNKS2, FAM45B, LOC723972, GAS7, RHBDD2 and CAMKK1. Subsequently, the most functionally enriched genes with the top 100 DM CpG sites were significantly (p ≤ 0.05) associated with SH2 domain binding, regulation of transcription, DNA-templated, nucleus, positive regulation of protein targeting to mitochondrion, nucleoplasm, Swr1 complex, histone exchange, and cellular response to organic substance. In addition, NLK, CAMKK1, LPAR2, CASP1, and NHS showed to be the most common regulators in the signaling network analysis. Taken together, these findings shed light on the methylation status of keloids that could be implicated in the underlying mechanism of keloid scars formation and remission.

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“…Studies have reported that ethanol-induced apoptosis serves a key role in the pathogenesis of ACM (26–29). A study on the mechanism of ethanol-induced cardiomyocyte apoptosis demonstrated that the levels of tumor necrosis factor-α, the apoptotic protein Bcl-2-associated X and caspase-3 are significantly increased in ACM (30). In the present study, AC16 cardiomyocytes were treated with ethanol and its effects on apoptosis analyzed.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑186‑5p is expressed highly in ethanol‑induced cardiomyocytes and regulates apoptosis via the target gene XIAP

Liu

2019

Mol Med Report

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Ethanol has a toxic effect on the heart, resulting in cardiomyocyte damage. Long-term high intake of ethanol leads to a non-ischemic dilated cardiomyopathy termed alcoholic cardiomyopathy (ACM). However, the pathogenesis of alcoholic cardiomyopathy remains unclear. The apoptosis of cardiomyocytes serves an important role in the pathogenesis of ACM. X-linked inhibitor of apoptosis protein (XIAP) is an important anti-apoptotic protein in human tissue cells. To the best of our knowledge, no studies have reported on its function in ethanol-induced cardiomyopathy. Previous works have screened the ACM-associated differentially expressed microRNAs (miRs), including miR-186-5p and miR-488-3p. TargetScan bioinformatics software was used to predict 949 target genes associated with miR-186-5p, and XIAP was demonstrated to be a target of miR-186-5p. The present study firstly analyzed the levels of apoptosis in ethanol-treated cardiomyocytes using flow cytometry. Alterations in the expression levels of miR-186-5p and XIAP were subsequently evaluated in ethanol-treated AC16 cardiomyocytes to assess the specific molecular mechanisms of ethanol-induced cardiomyocyte apoptosis. The levels of apoptosis in AC16 cardiomyocytes increased following ethanol treatment, and further increased with the rise in concentration and action time of ethanol. The expression levels of miR-186-5p were upregulated, and the expression levels of XIAP were downregulated in ethanol-treated cardiomyocytes. miR-186-5p may regulate ethanol-induced apoptosis in cardiomyocytes using XIAP as the direct target gene. This study provides a novel therapeutic target for the prevention and treatment of ACM.

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Association of caspase-1 polymorphisms with Chagas cardiomyopathy among individuals in Santa Cruz, Bolivia

Cited by 6 publications

References 37 publications

CASP1 Gene Polymorphisms and BAT1-NFKBIL-LTA-CASP1 Gene–Gene Interactions Are Associated with Restenosis after Coronary Stenting

CASP1 Gene Polymorphisms and BAT1-NFKBIL-LTA-CASP1 Gene–Gene Interactions Are Associated with Restenosis after Coronary Stenting

Identification of Differentially Methylated CpG Sites in Fibroblasts from Keloid Scars

MicroRNA‑186‑5p is expressed highly in ethanol‑induced cardiomyocytes and regulates apoptosis via the target gene XIAP

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