Mitochondrial DNA Mutations and Rheumatic Heart Diseases

• Main Authors: Fatou Balla Wade, Marie Parsine Sall, Fatimata Mbaye, Mbacké Sembene
• Format: Article
• Language: English
• Published: MDPI AG 2019-10-01
• Series: Journal of Cardiovascular Development and Disease
• Subjects: acute rheumatic fever; rheumatic heart diseases; <i>mt-cyb</i>; mutation; senegal
• Online Access: https://www.mdpi.com/2308-3425/6/4/36

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 Cardiovascular Surgery of Fann National University Hospital Centre, Dakar, Senegal (control group, healthy individuals) and sequenced. More than half of the <i>MT-CYB</i> 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 <i>MT-CYB</i> polymorphisms (7.14 &#177; 14.70 mutations per sample) and accounted for 72.73% of mutations. Paradoxically, subjects undergoing valvular replacement harbored infrequent polymorphisms (1.39 &#177; 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 <i>MT-CYB</i> mutations and ARF and its complications (i.e., RHDs) and that these mutations are largely deleterious.