Insulin receptor substrate-2 (IRS-2) plays critical role in the regulation of various metabolic processes by insulin and IGF-1. The defects in its expression and/or function are linked to diseases like polycystic ovary syndrome (PCOS), insulin resistance and cancer. To predict the transcription factors (TFs) responsible for the regulation of human IRS-2 gene expression, the transcription factor binding sites (TFBS) and the corresponding TFs were investigated by analysis of IRS-2 promoter sequence using MatInspector Genomatix software (Cartharius et al., 2005 [1]). The ibid data is part of author׳s publication (Anjali et al., 2015 [2]) that explains Follicle stimulating hormone (FSH) mediated IRS-2 promoter activation in human granulosa cells and its importance in the pathophysiology of PCOS. Further analysis was carried out for binary interactions of TF regulatory genes in IRS-2 network using Cytoscape software tool and R-code. In this manuscript, we describe the methodology used for the identification of TFBSs in human IRS-2 promoter region and provide details on experimental procedures, analysis method, validation of data and also the raw files. The purpose of this article is to provide the data on all TFBSs in the promoter region of human IRS-2 gene as it has the potential for prediction of the regulation of IRS-2 gene in normal or diseased cells from patients with metabolic disorders and cancer.
Aims Reduced psychological health is associated with adverse patient outcomes and higher mortality. We aimed to examine if a Brugada syndrome (BrS) diagnosis and symptomatic disease presentation were associated with an increased risk of new-onset depression or anxiety and all-cause mortality. Methods and results All Danish patients diagnosed with BrS (2006–2018) with no history of psychiatric disease and available for ≥6 months follow-up were identified using nationwide registries and followed for up to 5 years after diagnosis. The development of clinical depression or anxiety was evaluated using the prescription of medication and diagnosis codes. Factors associated with developing new-onset depression or anxiety were determined using a multivariate Cox proportional hazards regression model. Disease manifestation was categorized as symptomatic (aborted cardiac arrest, ventricular tachycardia, or syncope) or asymptomatic/unspecified at diagnosis. A total of 223 patients with BrS and no history of psychiatric disease were identified (72.6% male, median age at diagnosis 46 years, 45.3% symptomatic). Of these, 15.7% (35/223) developed new-onset depression or anxiety after BrS diagnosis (median follow-up 5.0 years). A greater proportion of symptomatic patients developed new-onset depression or anxiety compared with asymptomatic patients [21/101 (20.8%) and 14/122 (11.5%), respectively, P = 0.08]. Symptomatic disease presentation (HR 3.43, 1.46–8.05) and older age (lower vs. upper tertile: HR 4.41, 1.42–13.63) were significantly associated with new-onset depression or anxiety. All-cause mortality in this group of patients treated according to guidelines was low (n = 4, 1.8%); however, 3/4 developed depression or anxiety before death. Conclusion Approximately, one-sixth of patients with BrS developed new-onset depression or anxiety following a diagnosis of BrS. Symptomatic BrS disease manifestation was significantly associated with new-onset depression or anxiety.
Funding Acknowledgements Type of funding sources: None. Background To lower the risk of sudden cardiac death, patients with Brugada Syndrome (BrS) are recommended to avoid intake of drugs known to increase the risk of arrhythmias or the development of type-1 BrS ECG. However, information on adherence to these recommendations among patients with BrS is limited. Purpose To examine treatment with non-recommended drugs before and after diagnosis with BrS, risk factors of treatment with these drugs, and whether treatment was associated with a higher risk of hospitalization with ventricular arrhythmias or death. Methods All patients diagnosed with BrS in Denmark (1995-2018) with >12 months of follow-up were identified through nationwide registries using the ICD-10 diagnosis code DI472M (PPV 95.8%). Relevant BrS risk drugs were identified and grouped as drugs to "avoid" or "preferably avoid" in agreement with the likelihood of promoting arrhythmias and type-1 BrS ECG according to brugadadrugs.org(1) (accessed August 2021). Multiple logistic regression (adjusted for sex, age, year of diagnosis, and relevant comorbidities and drugs) was performed to identify factors associated with risk drug use during follow-up. Results We identified 270 patients with BrS. Median age at the time of diagnosis was 46.2 years [IQR 32.6-57.6], 70.4% were male. Before the time of diagnosis, 16 patients (5.9%) were treated with a drug to "avoid" or "preferably avoid" (n=5 and n=12, respectively). During a median follow-up of 79 months, 89 patients (33%) were treated with at least one BrS risk drug after the time of diagnosis (table). A total of 22 patients with BrS (8.1%) received ≥2 different drugs at any time during follow-up. There was no significant difference in proportions of patients receiving a risk drug the year prior to diagnosis (12.2%) compared to each of the five years following diagnosis (year 1-5, respectively: 12.2%; 9.7%; 12.3%; 13.6%; 13.5% (p>0.05 for all)). Females had an odds ratio (OR) of 2.21 [95% CI 1.21-4.03] for use of risk drugs. Also associated with a greater likelihood of risk drug use after diagnosis were having a psychiatric disease at baseline (OR=4.80 [1.72-13.41]) and any use of a risk drug within 90 days prior to diagnosis (OR=8.54 [2.13-34.31]) (figure). During follow-up, six patients were hospitalized for ventricular arrhythmias; none had redeemed a prescription of a risk drug. In total, 12 patients died, of which five (41.7%) had redeemed a prescription of one or more risk drugs within 50 days of death. Conclusions 1/3 patients with BrS received a risk drug at any time point after diagnosis. No change in proportions of patients treated with risk drugs was identified after time of diagnosis. 5/12 patients that died during follow-up had redeemed a prescription of one or more risk drugs within 50 days of death. Female sex, any psychiatric diagnosis, and use of a non-recommended drug before diagnosis with BrS were associated with a greater likelihood of risk drug use after diagnosis.
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