Dataset Information

Association of rs2070600 in advanced glycosylation end-product specific receptor with prognosis of heart failure.

ABSTRACT:

Aims

Our objective was to investigate the association of common variants in the coding region of advanced glycosylation end-product specific receptor (RAGE) and the prognosis of heart failure (HF).

Methods and results

A total of 3394 HF patients were continuously enrolled from January 2009 to August 2018 with a median follow-up of 20.4 months. Additionally, 2861 healthy subjects also participated in the study. By sequencing these two groups, we identified a common functional missense variant rs2070600 in the coding region of RAGE, which showed a significant association with the prognosis of HF [hazard ratio = 0.53, 95%, confidence interval (CI) = 0.30-0.94, P = 0.03], but no association with the risk of HF (odds ratio = 0.52, 95%, CI = 0.66-1.04, P = 0.106). A series of functional assays revealed that rs2070600-A, but not -G allele, suppressed the expression of RAGE protein by facilitating the binding of miR-125a-3p. Furthermore, the RAGE messenger RNA levels of human peripheral blood lymphocytes were reduced in subjects with the rs2070600-AA genotype compared with subjects with the rs2070600-GG or -AG genotypes. Additionally, our Western blot results from human heart tissue showed increased RAGE expression in HF samples compared with that in healthy donors.

Conclusions

Our results demonstrate that the common missense variant rs2070600-A allele is associated with a reduced risk of cardiovascular death and cardiac transplantation by facilitating the binding of miR-125a-3p.

SUBMITTER: Li S

PROVIDER: S-EPMC7755010 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

Association of rs2070600 in advanced glycosylation end-product specific receptor with prognosis of heart failure.

Li Shiyang S Hu Dong D Hu Senlin S Sun Yang Y Zhang Ying Y Li Huihui H Chen Yanghui Y Liu Hao H Cui Guanglin G Wang Dao Wen DW

ESC heart failure 20200910 6

<h4>Aims</h4>Our objective was to investigate the association of common variants in the coding region of advanced glycosylation end-product specific receptor (RAGE) and the prognosis of heart failure (HF).<h4>Methods and results</h4>A total of 3394 HF patients were continuously enrolled from January 2009 to August 2018 with a median follow-up of 20.4 months. Additionally, 2861 healthy subjects also participated in the study. By sequencing these two groups, we identified a common functional misse ...[more]

PMID: 32914565

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Project description:BackgroundAdvanced glycation end products (AGEs) promote adverse health effects and may contribute to the multi-system functional decline observed in aging. Diet is a major source of AGEs, and foods high in protein may increase circulating AGE concentrations. However, epidemiological evidence that high-protein diets increase AGEs is lacking.ObjectivesWe examined whether dietary protein intake was associated with serum concentrations of the major AGE carboxymethyl-lysine (CML) and the soluble receptor for AGEs (sRAGE) in 2439 participants from the Health, Aging, and Body Composition study (mean age, 73.6 ± 2.9 y; 52% female; 37% black).MethodsCML and sRAGE were measured by ELISA, and the CML/sRAGE ratio was calculated. Protein intake was estimated using an interviewer-administered FFQ and categorized based on current recommendations for older adults: <0.8 g/kg/d (n = 1077), 0.8 to <1.2 g/kg/d (n = 922), and ≥1.2 g/kg/d (n = 440). Associations between protein intake and AGE-RAGE biomarkers were examined using linear regression models adjusted for demographics, height, lifestyle behaviors, prevalent disease, cognitive function, inflammation, and other dietary factors.ResultsCML concentrations were higher in individuals with higher total protein intake (adjusted least squares mean ± SE: <0.8 g/kg/d, 829 ± 17 ng/ml; 0.8 to <1.2 g/kg/d, 860 ± 15 ng/ml; ≥1.2 g/kg/d, 919 ± 23 ng/ml; P for trend = 0.001), as were sRAGE concentrations (<0.8 g/kg/d, 1412 ± 34 pg/ml; 0.8 to <1.2 g/kg/d, 1479 ± 31 pg/ml; ≥1.2 g/kg/d, 1574 ± 47 pg/ml; P for trend < 0.0001). Every 0.1 g/kg/d increment in total protein intake was associated with a 13.3 ± 3.0 ng/ml increment in CML and a 22.1 ± 6.0 pg/ml increment in sRAGE (P < 0.0001 for both). Higher CML and sRAGE concentrations were also associated with higher intakes of both animal and vegetable protein (all P values ≤ 0.01). There were no significant associations with the CML/sRAGE ratio.ConclusionsHigher dietary protein intake was associated with higher CML and sRAGE concentrations in older adults; however, the CML/sRAGE ratio remained similar across groups.

Project description:Objectives: The aim of this study was to investigate whether echocardiographic assessment of myocardial work is a predictor of outcome in advanced heart failure. Background: Global work index (GWI) and global constructive work (GCW) are calculated by means of speckle tracking, blood pressure measurement, and a normalized reference curve. Their prognostic value in advanced heart failure is unknown. Methods: Cardiopulmonary exercise testing and echocardiography with assessment of GWI and GCW was performed in patients with advanced heart failure caused by ischemic heart disease or dilated cardiomyopathy (n = 105). They were then followed up repeatedly. The combined endpoint was all-cause death, implantation of a left ventricular assist device, or heart transplantation. Results: The median patient age was 54 years (interquartile range [IQR]: 48-59.9). The mean left ventricular ejection fraction was 27.8 ± 8.2%, the median NT-proBNP was 1,210 pg/ml (IQR: 435-3,696). The mean GWI was 603 ± 329 mmHg% and the mean GCW was 742 ± 363 mmHg%. The correlation between peak oxygen uptake and GWI as well as GCW was strongest in patients with ischemic cardiomyopathy (r = 0.56, p = 0.001 and r = 0.53, p = 0.001, respectively). The median follow-up was 16 months (IQR: 12-18.5). Thirty one patients met the combined endpoint: Four patients died, eight underwent transplantation, and 19 underwent implantation of a left ventricular assist device. In the multivariate Cox regression analysis, only NYHA class, NT-proBNP and GWI (hazard ratio [HR] for every 50 mmHg%: 0.85; 95% CI: 0.77-0.94; p = 0.002) as well as GCW (HR for every 50 mmHg%: 0.86; 95% CI: 0.79-0.94; p = 0.001) were identified as independent predictors of the endpoint. The cut-off value for predicting the outcome was 455 mmHg% for GWI (AUC: 0.80; p < 0.0001; sensitivity 77.4%; specificity 71.6%) and 530 mmHg% for GCW (AUC: 0.80; p < 0.0001; sensitivity 74.2%; specificity 78.4%). Conclusions: GWI and GCW are powerful predictors of outcome in patients with advanced heart failure.

Dataset Information

Association of rs2070600 in advanced glycosylation end-product specific receptor with prognosis of heart failure.

Aims

Methods and results

Conclusions

Publications

Association of rs2070600 in advanced glycosylation end-product specific receptor with prognosis of heart failure.

Similar Datasets

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