Dataset Information

Mitochondrial DNA Mutations and Rheumatic Heart Diseases.

ABSTRACT: Acute rheumatic fever (ARF) is an autoimmune disease affecting the heart-valve endocardium in its final stage. Although rare in developing countries, ARF persists in third-world countries, particularly Senegal, where rheumatic heart diseases (RHDs) are the most common pediatric cardiovascular pathology. This study aimed to investigate mutations in MT-CYB in ARF and RHD in Senegalese patients. MT-CYB was amplified from blood samples from ARF patients at the Clinical of Thoracic and Cardiovascular Surgery of Fann National University Hospital Centre, Dakar, Senegal (control group, healthy individuals) and sequenced. More than half of the MT-CYB mutations (58.23%) were heteroplasmic. Transitions (61.67%) were more frequent than transversions (38.33%), and non-synonymous substitutions represented 38.33% of mutations. Unoperated RHD patients harbored frequent MT-CYB polymorphisms (7.14 ± 14.70 mutations per sample) and accounted for 72.73% of mutations. Paradoxically, subjects undergoing valvular replacement harbored infrequent polymorphisms (1.39 ± 2.97 mutations per patient) and lacked 36 mutations present in unoperated subjects. A genetic differentiation was observed between these two populations, and the mutations in operated subjects were neutral, while those in unoperated subjects were under positive selection. These results indicate a narrow link (perhaps even causal) between MT-CYB mutations and ARF and its complications (i.e., RHDs) and that these mutations are largely deleterious.

SUBMITTER: Wade FB

PROVIDER: S-EPMC6956112 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Mitochondrial DNA Mutations and Rheumatic Heart Diseases.

Wade Fatou Balla FB Sall Marie Parsine MP Mbaye Fatimata F Sembene Mbacké M

Journal of cardiovascular development and disease 20191011 4

Acute rheumatic fever (ARF) is an autoimmune disease affecting the heart-valve endocardium in its final stage. Although rare in developing countries, ARF persists in third-world countries, particularly Senegal, where rheumatic heart diseases (RHDs) are the most common pediatric cardiovascular pathology. This study aimed to investigate mutations in <i>MT-CYB</i> in ARF and RHD in Senegalese patients. <i>MT-CYB</i> was amplified from blood samples from ARF patients at the Clinical of Thoracic and ...[more]

PMID: 31614609

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Project description:ObjectiveTo assess CXC chemokine receptor 5 (CXCR5) circulating DNA methylation differences in autoimmune rheumatic diseases and their relation with clinical features.MethodsTargeted methylation sequencing was performed using peripheral blood from 164 rheumatoid arthritis (RA), 30 systemic lupus erythematosus (SLE), 30 ankylosing spondylitis (AS), 30 psoriatic arthritis (PsA), 24 Sjögren's syndrome (SS) patients, and 30 healthy controls (HC).ResultsSignificant differences in CXCR5 cg19599951 methylation were found between RA and HC, as well as AS and SLE. RA patients exhibited higher methylation than HC and AS (p < 0.01) but lower than SLE (p < 0.05). SLE patients showed higher methylation compared to HC, AS, and PsA (p < 0.001, 0.01, and 0.05, respectively). No significant differences were found in patients with SS compared to other autoimmune diseases and HC. Methylation at cg19599951_103 (r = 0.17, p < 0.05) and cg19599951_209 (r = 0.22, p < 0.01), along with the CC haplotype (r = 0.21, p < 0.01), showed significant positive correlations with erythrocyte sedimentation rate (ESR), while the CT (r = -0.27, p < 0.001) and TT haplotypes (r = -0.19, p < 0.05) were negatively correlated. For C-reactive protein (CRP), methylation at cg19599951_103 (r = 0.29, p < 0.001) and cg19599951_209 (r = 0.33, p < 0.0001), and the CC haplotype (r = 0.34, p < 0.0001) was positively correlated, whereas the CT (r = -0.36, p < 0.0001) and TT (r = -0.30, p < 0.0001) haplotypes were negatively correlated. Significant negative correlations were observed between the CT haplotype and rheumatoid factor (r = -0.25, p < 0.01), and anti-citrullinated protein antibody (r = -0.20, p < 0.05). No significant correlations were found in patients with SLE, AS, and SS. Receiver operating characteristic analysis showed CXCR5 methylation could classify patients with RA versus those with AS (AUC: 0.624-0.967).ConclusionDifferential circulating CXCR5 methylation levels were observed in autoimmune rheumatic diseases, which correlated with inflammatory mediators in RA and may serve as potential biomarkers for RA diagnosis.

Dataset Information

Mitochondrial DNA Mutations and Rheumatic Heart Diseases.

Publications

Mitochondrial DNA Mutations and Rheumatic Heart Diseases.

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