**1. Introduction**

Acute rheumatic fever (ARF) is a major cause of cardiac disease and premature death in numerous regions worldwide [1]. ARF and rheumatic heart disease (RHD) have a high prevalence in developing countries in contrast with developed countries where these diseases have largely regressed [2]. ARF results in high morbidity and mortality rates worldwide and its incidence is the highest in Sub-Saharan Africa [3]. ARF incidence in developing countries exceeds 50 per 100,000 children [4]. In Senegal, RHD is the most prominent pediatric cardiovascular pathology [5].

Mutations in numerous genes, particularly those encoding immunity-related factors, are associated with ARF and RHD [6]. Genes encoding pattern recognition receptors belonging to the innate immune system, including ficolin [7], have been investigated. Genes encoding several cytokines including TNF-α or IL-6/-10 were reported to promote or aggravate ARF in studies in Mexico [8,9], Turkey [10], and Egypt [11].

On the other hand, it has been shown that the decrease in oxidative phosphorylation [12] Khatami mainly affects energy-intensive tissues, such as muscles, brain, heart, liver, and kidneys. This mechanism allows the production of ATP by the mitochondrial respiratory chain [13]. *MT-CYB* encodes the cytochrome b protein, which is the only subunit of the respiratory complex III (one of the five complexes of the respiratory chain), encoded by mitochondrial DNA, the others being of

> 3

nuclear origin [13]. Cytochrome b plays a central role in the production of ATP [12] and as a catalytic subunit binding to the substrate of quinone and facilitating the transmission of electrons to cytochrome c [14]. Many mutations of *MT-CYB*, identified so far, are related to diseases such as stress intolerance, myopathies, cardiomyopathies, and neuropathies. These mutations generally show a deficit of enzymatic activity and a decrease in the number of certain subunits of complex III [13]. Mitochondrial dysfunction is characteristic of heart failure [15].

Thus far, no study on the mitochondrial genome has focused on ARF and RHD, and genetic investigations of these pathologies has not been carried out in Senegal. Hence, we hypothesized that mitochondrial *MT-CYB* mutations influence the occurrence and/or complications in ARF. This study aimed to investigate mutations in *MT-CYB* in ARF and RHD in Senegalese patients. The following were the objectives of our study: (1) To investigate *MT-CYB* polymorphisms in ARF; (2) to evaluate the genetic diversity of *MT-CYB* in ARF; (3) to determine the genetic structure of *MT-CYB* based on populations; (4) to identify the type of *MT-CYB* mutations in ARF.

#### **2. Materials and Methods**
