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• W2087280330 abstract "PurposeCommon genetic variants at 1p36 (rs1739843), 6p21 (rs9262636) and 10q26 (rs2234962) show replicated associations with heart failure (HF) risk. We hypothesized that these variants would associate with HF severity and clinical outcomes in chronic HF.MethodsWe performed genome-wide genotyping in a subcohort of 1334 genetically-inferred Caucasians of a multi-center cohort of chronic HF outpatients. We used multivariable regression models to test the association between risk alleles at rs1739843, rs9262636, and rs2234962 and measures of cardiac remodeling (ejection fraction, EF; left ventricular end-diastolic dimension index, LVEDDI), NYHA class, and markers of HF severity (systolic blood pressure; serum sodium, SNa; brain natriuretic peptide; soluble toll-like receptor 2). Associations between variants and the composite endpoint of time to heart transplantation, ventricular assist device implantation, or all-cause death were assessed using Cox regression models. Subgroup analyses were performed stratified by HF etiology.ResultsThe rs1739843 variant, which is in linkage disequilibrium with a common variant in the CLCNKA renal chloride channel, associated with SNa [+0.34 mEq/L, 95% CI: (0.07 to 0.60), p=0.014], but not with other cross-sectional measures or outcomes. The rs9262636 variant, which lies within the major histocompatibility complex region, showed no statistically significant associations in cross-sectional or outcome analyses. The rs2234962 variant, a non-synonymous variant in the cytoprotective protein BAG3, associated with EF [-3.2%, 95% CI (-1.6 to - 4.5), p<0.001] and LVEDDI [+0.9 mm/m2, 95% CI (0.2 to 1.6), p=0.012]. A priori stratified analyses by HF etiology revealed associations among the non-ischemic subgroup only [EF -4.9%, 95% CI: (-2.7 to -7.2), p<0.001; LVEDDI 1.4 mm/m2, 95% CI: (0.2 to 2.1), p=0.016]. The rs2234962 variant was not associated with clinical outcomes.ConclusionThe rs2234962 variant in BAG3, a cytoprotective co-chaperone involved in myocyte integrity, shows significant associations with indexes of ventricular remodeling, particularly in non-ischemic HF. Although variants at all 3 loci are associated with HF risk, they do not have meaningful effects on clinical outcomes. PurposeCommon genetic variants at 1p36 (rs1739843), 6p21 (rs9262636) and 10q26 (rs2234962) show replicated associations with heart failure (HF) risk. We hypothesized that these variants would associate with HF severity and clinical outcomes in chronic HF. Common genetic variants at 1p36 (rs1739843), 6p21 (rs9262636) and 10q26 (rs2234962) show replicated associations with heart failure (HF) risk. We hypothesized that these variants would associate with HF severity and clinical outcomes in chronic HF. MethodsWe performed genome-wide genotyping in a subcohort of 1334 genetically-inferred Caucasians of a multi-center cohort of chronic HF outpatients. We used multivariable regression models to test the association between risk alleles at rs1739843, rs9262636, and rs2234962 and measures of cardiac remodeling (ejection fraction, EF; left ventricular end-diastolic dimension index, LVEDDI), NYHA class, and markers of HF severity (systolic blood pressure; serum sodium, SNa; brain natriuretic peptide; soluble toll-like receptor 2). Associations between variants and the composite endpoint of time to heart transplantation, ventricular assist device implantation, or all-cause death were assessed using Cox regression models. Subgroup analyses were performed stratified by HF etiology. We performed genome-wide genotyping in a subcohort of 1334 genetically-inferred Caucasians of a multi-center cohort of chronic HF outpatients. We used multivariable regression models to test the association between risk alleles at rs1739843, rs9262636, and rs2234962 and measures of cardiac remodeling (ejection fraction, EF; left ventricular end-diastolic dimension index, LVEDDI), NYHA class, and markers of HF severity (systolic blood pressure; serum sodium, SNa; brain natriuretic peptide; soluble toll-like receptor 2). Associations between variants and the composite endpoint of time to heart transplantation, ventricular assist device implantation, or all-cause death were assessed using Cox regression models. Subgroup analyses were performed stratified by HF etiology. ResultsThe rs1739843 variant, which is in linkage disequilibrium with a common variant in the CLCNKA renal chloride channel, associated with SNa [+0.34 mEq/L, 95% CI: (0.07 to 0.60), p=0.014], but not with other cross-sectional measures or outcomes. The rs9262636 variant, which lies within the major histocompatibility complex region, showed no statistically significant associations in cross-sectional or outcome analyses. The rs2234962 variant, a non-synonymous variant in the cytoprotective protein BAG3, associated with EF [-3.2%, 95% CI (-1.6 to - 4.5), p<0.001] and LVEDDI [+0.9 mm/m2, 95% CI (0.2 to 1.6), p=0.012]. A priori stratified analyses by HF etiology revealed associations among the non-ischemic subgroup only [EF -4.9%, 95% CI: (-2.7 to -7.2), p<0.001; LVEDDI 1.4 mm/m2, 95% CI: (0.2 to 2.1), p=0.016]. The rs2234962 variant was not associated with clinical outcomes. The rs1739843 variant, which is in linkage disequilibrium with a common variant in the CLCNKA renal chloride channel, associated with SNa [+0.34 mEq/L, 95% CI: (0.07 to 0.60), p=0.014], but not with other cross-sectional measures or outcomes. The rs9262636 variant, which lies within the major histocompatibility complex region, showed no statistically significant associations in cross-sectional or outcome analyses. The rs2234962 variant, a non-synonymous variant in the cytoprotective protein BAG3, associated with EF [-3.2%, 95% CI (-1.6 to - 4.5), p<0.001] and LVEDDI [+0.9 mm/m2, 95% CI (0.2 to 1.6), p=0.012]. A priori stratified analyses by HF etiology revealed associations among the non-ischemic subgroup only [EF -4.9%, 95% CI: (-2.7 to -7.2), p<0.001; LVEDDI 1.4 mm/m2, 95% CI: (0.2 to 2.1), p=0.016]. The rs2234962 variant was not associated with clinical outcomes. ConclusionThe rs2234962 variant in BAG3, a cytoprotective co-chaperone involved in myocyte integrity, shows significant associations with indexes of ventricular remodeling, particularly in non-ischemic HF. Although variants at all 3 loci are associated with HF risk, they do not have meaningful effects on clinical outcomes. The rs2234962 variant in BAG3, a cytoprotective co-chaperone involved in myocyte integrity, shows significant associations with indexes of ventricular remodeling, particularly in non-ischemic HF. Although variants at all 3 loci are associated with HF risk, they do not have meaningful effects on clinical outcomes." @default.
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• W2087280330 date "2015-04-01" @default.
• W2087280330 modified "2023-10-18" @default.
• W2087280330 title "BAG3 Variant Is Associated With Ventricular Remodeling But Not Clinical Outcomes in Chronic Heart Failure" @default.
• W2087280330 doi "https://doi.org/10.1016/j.healun.2015.01.480" @default.
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