Dataset Information

FNDC5 genetic polymorphism in patients with peripartum cardiomyopathy.

ABSTRACT:

Background

Late in pregnancy or soon after delivery, peripartum cardiomyopathy (PPCM) which is an uncommon type of cardiomyopathy, can develop. To assess the association between the level of irisin expression and (FNDC5) (rs3480) gene polymorphism with peripartum cardiomyopathy.

Methods

This is a case control study included a thirty female patients with new-onset PPCM and sixty healthy females at the at the peripartum period in same time window for PPCM as a control. For each patient, comprehensive medical history was taken, full clinical assessment was done, ECHO., FNDC5 (rs3480) & Irisin assay.

Results

The left ventricle end diastolic dimensions &left atrium diameters were statistically significant higher in patients' group than controls' group (P=0.000 for all), Also left ventricular ejection fraction (%) was statistically significant lower in patients than controls and as regards irisin, its Mean ±SD was lower in patient group than control group (8.44±1.1 vs 10.65±2.31) with (p <0.001) which is considered a significant difference statistically.

Conclusion

Irisin level was lower in peripartum cardiomyopathic patients when compared with normal individuals and regarding its genotype, the homotype A/A was higher than homotype G/G.

SUBMITTER: Altaher AM

PROVIDER: S-EPMC10921118 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

FNDC5 genetic polymorphism in patients with peripartum cardiomyopathy.

Altaher Ali Mohamad AM Eid Mohamed M Moslem Hesham H H Ali Amal A Mustafa Samar S Foad Amera Morad AM

Caspian journal of internal medicine 20240101 1

<h4>Background</h4>Late in pregnancy or soon after delivery, peripartum cardiomyopathy (PPCM) which is an uncommon type of cardiomyopathy, can develop. To assess the association between the level of irisin expression and (FNDC5) (rs3480) gene polymorphism with peripartum cardiomyopathy.<h4>Methods</h4>This is a case control study included a thirty female patients with new-onset PPCM and sixty healthy females at the at the peripartum period in same time window for PPCM as a control. For each pati ...[more]

PMID: 38463931

Similar Datasets

Project description:BackgroundPeripartum cardiomyopathy (PPCM) occurs in ≈1:2000 deliveries in the United States and worldwide. The genetic underpinnings of PPCM remain poorly defined. Approximately 10% of women with PPCM harbor truncating variants in TTN (TTNtvs). Whether mutations in other genes can predispose to PPCM is not known. It is also not known if the presence of TTNtvs predicts clinical presentation or outcomes. Nor is it known if the prevalence of TTNtvs differs in women with PPCM and preeclampsia, the strongest risk factor for PPCM.MethodsWomen with PPCM were retrospectively identified from several US and international academic centers, and clinical information and DNA samples were acquired. Next-generation sequencing was performed on 67 genes, including TTN, and evaluated for burden of truncating and missense variants. The impact of TTNtvs on the severity of clinical presentation, and on clinical outcomes, was evaluated.ResultsFour hundred sixty-nine women met inclusion criteria. Of the women with PPCM, 10.4% bore TTNtvs (odds ratio=9.4 compared with 1.2% in the reference population; Bonferroni-corrected P [P*]=1.2×10-46). We additionally identified overrepresentation of truncating variants in FLNC (odds ratio=24.8, P*=7.0×10-8), DSP (odds ratio=14.9, P*=1.0×10-8), and BAG3 (odds ratio=53.1, P*=0.02), genes not previously associated with PPCM. This profile is highly similar to that found in nonischemic dilated cardiomyopathy. Women with TTNtvs had lower left ventricular ejection fraction on presentation than did women without TTNtvs (23.5% versus 29%, P=2.5×10-4), but did not differ significantly in timing of presentation after delivery, in prevalence of preeclampsia, or in rates of clinical recovery.ConclusionsThis study provides the first extensive genetic and phenotypic landscape of PPCM and demonstrates that predisposition to heart failure is an important risk factor for PPCM. The work reveals a degree of genetic similarity between PPCM and dilated cardiomyopathy, suggesting that gene-specific therapeutic approaches being developed for dilated cardiomyopathy may also apply to PPCM, and that approaches to genetic testing in PPCM should mirror those taken in dilated cardiomyopathy. Last, the clarification of genotype/phenotype associations has important implications for genetic counseling.

Project description:BackgroundRight ventricular (RV) dysfunction predicts adverse outcome in peripartum cardiomyopathy (PPCM). We recently demonstrated beneficial effects associated with the prolactin release inhibitor bromocriptine at different doses when added to standard heart failure therapy in PPCM. Here, we evaluated for the first time the therapeutic potential of bromocriptine particularly in PPCM patients with RV involvement.MethodsIn this study, 40 patients with PPCM were included, of whom 24 patients had reduced RV ejection fraction (RVEF < 45%). We examined the effect of short-term (1W: bromocriptine, 2.5 mg, 7 days, n = 10) compared with long-term bromocriptine treatment (8W: 5 mg for 2 weeks followed by 2.5 mg for another 6 weeks, n = 14) in addition to guideline-based heart failure therapy in patients with an initial RVEF < 45% on the following outcomes: (1) change from baseline (Δ delta) in RVEF, (2) change from baseline in left ventricular EF (LVEF), and (3) rate of patients with full LV recovery (LVEF ≥ 50%) and (4) rate of patients with full RV recovery (RVEF ≥ 55%) at 6-month follow-up as assessed by cardiac magnetic resonance imaging.ResultsReduced RVEF at initial presentation was associated with a lower rate of full cardiac recovery at 6-month follow-up (patients with RV dysfunction: 58% vs. patients with normal RV function: 81%; p = 0.027). RVEF increased from 38 ± 7 to 53 ± 11% with a delta-RVEF of + 15 ± 12% in the 1W group, and from 35 ± 9 to 58 ± 7% with a Δ RVEF of + 23 ± 10% in the 8W group (Δ RVEF 1W vs 8W: p = 0.118). LVEF increased from 25 ± 8 to 46 ± 12% with a Δ LVEF of + 21 ± 11% in the 1W group, and from 22 ± 6 to 49 ± 10% with a Δ LVEF of + 27 ± 9% in the 8W group (Δ LVEF 1W vs 8W: p = 0.211). Full LV recovery was present in 50% of the 1W group and in 64% of the 8W group (p = 0.678). Full RV recovery was observed in 40% of the 1W group and in 79% of the 8W group (p = 0.092).ConclusionsDespite overall worse outcome in patients with RV dysfunction at baseline, bromocriptine treatment in PPCM patients with RV involvement was associated with a high rate of full RV and LV recovery, although no significant differences were observed between the short-term and long-term bromocriptine treatment regime. These findings suggest that bromocriptine in addition to standard heart failure therapy may be also effective in PPCM patients with biventricular impairment.

Project description:BackgroundPregnancy imposes significant cardiovascular adaptations, including progressive increases in plasma volume and cardiac output. For most women, this physiological adaptation resolves at the end of pregnancy, but some women develop pathological dilatation and ultimately heart failure late in pregnancy or in the postpartum period, manifesting as peripartum cardiomyopathy (PPCM). Despite the mortality risk of this form of heart failure, the molecular mechanisms underlying PPCM have not been extensively examined in human hearts.MethodsProtein and metabolite profiles from left ventricular tissue of end-stage PPCM patients (N=6-7) were compared with dilated cardiomyopathy (DCM; N=5-6) and nonfailing donors (N=7-18) using unbiased quantitative mass spectrometry. All samples were derived from the Sydney Heart Bank. Data are available via ProteomeXchange with identifier PXD055986. Differential protein expression and metabolite abundance and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed.ResultsProteomic analysis identified 2 proteins, SBSPON (somatomedin B and thrombospondin type 1 domain-containing protein precursor) and TNS3 (tensin 3), that were uniquely downregulated in PPCM. SBSPON, an extracellular matrix protein, and TNS3, involved in actin remodeling and cell signaling, may contribute to impaired tissue remodeling and fibrosis in PPCM. Metabolomic analysis revealed elevated levels of homogentisate and deoxycholate and reduced levels of lactate and alanine in PPCM, indicating disrupted metabolic pathways and glucose utilization. Both PPCM and DCM shared pathways related to inflammation, immune responses, and signal transduction. However, thyroid hormone signaling was notably reduced in PPCM, affecting contractility and calcium handling through altered expression of PLN (phospholamban) and Sarcoendoplasmic Reticulum Calcium ATPase (SERCA). Enhanced endoplasmic reticulum stress and altered endocytosis pathways in PPCM suggested additional mechanisms of energy metabolism disruption.ConclusionsThe present study reveals unique posttranslational molecular features of the PPCM myocardium, which mediates cellular and metabolic remodeling, and holds promise as potential targets for therapeutic intervention.

Dataset Information

FNDC5 genetic polymorphism in patients with peripartum cardiomyopathy.

Background

Methods

Results

Conclusion

Publications

FNDC5 genetic polymorphism in patients with peripartum cardiomyopathy.

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