The rs12526453 Polymorphism in an Intron of the PHACTR1 Gene and Its Association with 5-Year Mortality of Patients with Myocardial Infarction

Szpakowicz, Anna; Kiliszek, Marek; Pepiński, Witold; Waszkiewicz, Ewa; Franaszczyk, Maria; Skawrońska, Małgorzata; Płoski, Rafał; Niemcunowicz‐Janica, Anna; Burzyńska, Beata; Tulacz, Dorota; Maciejak, Agata; Kamiński, Marcin; Opolski, Grzegorz; Musiał, Włodzimierz J.; Kamiński, Karol

doi:10.1371/journal.pone.0129820

Cited by 15 publications

(6 citation statements)

References 28 publications

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“…In this study, our results further showed that GSDMD expression, an executor of pyroptosis, is significantly increased in gastric mucosa with H. pylori infection, which is in line with the result displayed that GSDMD is drastically decreased in gastric epithelial cells in response to rabeprazole stimulation, a regimen for H. pylori-infectious treatment. What's more, the inappropriate activation of the NLRP3 inflammasome could contribute to the onset and progression of various diseases [38], such as obesity [39], type 2 diabetes [40], inflammatory bowel disease [41], rheumatoid arthritis [42], liver fibrosis [43], Myocardial infarctions [44]. In addition to both NF-KB and SREBP-1c have been reported to regulate NLRPs transcription [17,18,20,45], the further work is required to address the mechanism through which rabeprazole regulated NLRP3, leading to inhibit NLRP3 inflammasome in future work.…”

Section: Discussionmentioning

confidence: 99%

Rabeprazole inhibits inflammatory reaction by inhibition of cell pyroptosis in gastric epithelial cells

Xie

Fan

Xiong

et al. 2021

BMC Pharmacol Toxicol

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Background Helicobacter pylori (H. pylori) is a common pathogen in development of peptic ulcers with pyroptosis. Rabeprazole, a critical component of standard triple therapy, has been widely used as the first-line regimen for H. pylori infectious treatment. The aim of this study to explore the function of Rabeprazole on cell pyroptosis in vitro. Methods The clinical sample from patients diagnosed with or without H. pylori-infection were collected to analyze by Immunohistochemistry (IHC). Real-time quantitative PCR (qPCR), western blot (WB) and enzyme linked immunosorbent assay (Elisa) were performed to analyze the effect of Rabeprazole on cell pyroptosis, including LDH, IL-1β and IL-18. Results In this study, we showed that Rabeprazole regulated a phenomenon of cell pyroptosis as confirmed by lactate dehydrogenase (LDH) assay. Further results showed that Rabeprazole inhibited cell pyroptosis in gastric epithelial cells by alleviating GSDMD-executed pyroptosis, leading to decrease IL-1β and IL-18 mature and secretion, which is attributed to NLRP3 inflammasome activation inhibition. Further analysis showed that ASC, NLRP3 and Caspase-1, was significantly repressed in response to Rabeprazole stimulation, resulting in decreasing cleaved-caspase-1 expression. Most important, NLRP3 and GSDMD is significantly increased in gastric tissue of patients with H. pylori infection. Conclusion These findings revealed a critical role of Rabeprazole in cell pyroptosis in patients with H. pylori infection, suggesting that targeting cell pyroptosis is an alternative strategy in improving H. pylori treatment.

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Section: Discussionmentioning

confidence: 99%

Rabeprazole inhibits inflammatory reaction by inhibition of cell pyroptosis in gastric epithelial cells

Xie

Fan

Xiong

et al. 2021

BMC Pharmacol Toxicol

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“…Lee et al found that cardiovascular mortality was higher in subjects with the rs4977574 GG genotype than in those with other genotypes 96 . The association between four SNPs on chromosome 9p21, CAD, and MI has been replicated several times in multiple populations [97][98][99][100] In patients with MI with ST-segment elevation Szpakowicz et al revealed association between the rs12526453 of the phosphatase and actin regulator 1 (PHACTR1) gene and 5-year mortality 101 . However, in another study, the DIO2 Thr92Ala polymorphism was not related with thyroid parameters, cognitive functioning and health-related quality of life 102 .…”

Section: Discussionmentioning

confidence: 95%

Importance of Thyroid Hormone level and Genetic Variations in Deiodinases for Patients after Acute Myocardial Infarction: A Longitudinal Observational Study

Kažukauskienė

Skiriutė

Gustienė

et al. 2020

Sci Rep

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This study aimed to examine the influence of thyroid hormone (TH) levels and genetic polymorphisms of deiodinases on long-term outcomes after acute myocardial infarction (AMI). In total, 290 patients who have experienced AMi were evaluated for demographic, clinical characteristics, risk factors, tH and NT-pro-BNP. Polymorphisms of TH related genes were included deiodinase 1 (DIO1) (rs11206244-C/T, rs12095080-A/G, rs2235544-A/C), deiodinase 2 (DIO2) (rs225015-G/A, rs225014-T/C) and deiodinase 3 (DIO3) (rs945006-T/G). Both all-cause and cardiac mortality was considered key outcomes. Cox regression model showed that NT-pro-BNP (HR = 2.11; 95% CI = 1.18-3.78; p = 0.012), the first quartile of fT3, and DIO1 gene rs12095080 were independent predictors of cardiac-related mortality (HR = 1.74; 95% CI = 1.04-2.91; p = 0.034). The DIO1 gene rs12095080 AG genotype (OR = 3.97; 95% ci = 1.45-10.89; p = 0.005) increased the risk for cardiac mortality. Lower fT3 levels and the DIO1 gene rs12095080 are both associated with cardiac-related mortality after AMI. Recent clinical research in cardiovascular disease as well as in coronary artery disease (CAD) has provided evidence that altered thyroid hormone (TH) metabolism, including low total triiodothyronine (T3) syndrome or pre-existing subclinical primary hypothyroidism, is an important indicator of adverse short-term and long-term outcomes, including mortality 1-5. These changes in thyroid homeostasis are known as "euthyroid sick syndrome" 6,7 or "non-thyroidal illness syndrome" (NTIS) 8,9 and are defined by low serum levels of free T3 (fT3), T3 and high levels of reverse T3 (rT3) followed by normal or low levels of thyroxine (T4) and thyroid-stimulating hormone (TSH). Low T3 syndrome is observed in about one third of patients following acute cardiovascular events and has been linked to the severity of the disease and its adverse prognosis 10. This syndrome has been established in patients with heart failure (HF) 11-14 , myocardial infarction (MI) 2,15-18 , and has been linked to the cardiac remodelling process 19-21 and poor prognosis 1,3,4,13,22,23. Studies suggest that variations of TH within clinically normal ranges, such as isolated reduction in fT3 level or higher level of free T4 (fT4), could constitute a model of abnormal TH metabolism. These variations could act as a risk factor for CAD, in a similar fashion to overt or subclinical hypothyroidism, thereby influencing the occurrence as well as severity of coronary atherosclerosis and its related outcomes 2,24-32 .

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“…It is generally recognized that CAD is a multifactorial disease [ 14 ]. The occurrence and development of CAD are influenced by environmental and genetic factors.…”

Section: Discussionmentioning

confidence: 99%

Associations of Rs3744841 and Rs3744843 Polymorphisms in Endothelial Lipase Gene with Risk of Coronary Artery Disease and Lipid Levels in a Chinese Population

Cai

Zhang

et al. 2016

PLoS ONE

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ObjectiveThe aim of the present study was to assess the association between the 2037T/C and 2237G/A polymorphisms in the EL gene and the risk of CAD and lipid levels in a Chinese population.MethodsA case-control study including 706 patients with CAD and 315 controls was performed. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to identify the genotypes.ResultsThe EL 2037 T/C polymorphism was associated with CAD risk and HDL-C levels. No significant differences were found between the EL 2237 G/A genotypes and CAD risk and lipid levels in the whole population. However, carriers of the 2237 A allele had higher Apo A1 levels than those with the 2237 GG genotype and in the CAD subgroup (P = 0.044). The CAD cases have a significantly lower frequency of the C-G haplotypes than the controls, and the T-A haplotype was significantly more common in the CAD patients than in the controls.ConclusionsOur study concluded that the EL 2037 T/C polymorphism was associated with CAD risk and HDL-C levels, and that the C allele might be a protective factor against CAD in the Chinese Han population. In addition, the EL 2237 A allele might be associated with an increased Apo A1 level in CAD subjects.

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The rs12526453 Polymorphism in an Intron of the PHACTR1 Gene and Its Association with 5-Year Mortality of Patients with Myocardial Infarction

Cited by 15 publications

References 28 publications

Rabeprazole inhibits inflammatory reaction by inhibition of cell pyroptosis in gastric epithelial cells

Rabeprazole inhibits inflammatory reaction by inhibition of cell pyroptosis in gastric epithelial cells

Importance of Thyroid Hormone level and Genetic Variations in Deiodinases for Patients after Acute Myocardial Infarction: A Longitudinal Observational Study

Associations of Rs3744841 and Rs3744843 Polymorphisms in Endothelial Lipase Gene with Risk of Coronary Artery Disease and Lipid Levels in a Chinese Population

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