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.

Is There a Link Between Nutrition, Genetics, and Cardiovascular Disease?

“…The first original article investigated MT-CYB mutations in acute rheumatic fever and rheumatic heart diseases among Senegalese patients. The authors of this study found a narrow link between MT-CYB mutations and acute rheumatic fever and its complications, i.e., rheumatic heart diseases [ 7 ]. In the second original study, conducted in Uruguay on two separate cohorts (children, n = 682; adolescents, n = 340), the authors tested potential associations between anthropometric parameters (i.e., weight, height and body mass index (BMI)) in early life stages and the state of the cardiovascular system in early childhood at the beginning of adulthood [ 8 ].…”