Genetic Susceptibility to Rheumatic Heart Disease: A Narrative Literature Review Highlighting Evidence From African Populations and Research Gaps in Sudan

Background and Aims: Rheumatic heart disease (RHD) remains a significant public health burden in low- and middle-income countries, particularly in sub-Saharan Africa. Although socioeconomic factors contribute to disease persistence, genetic susceptibility plays a critical role in determining progression from Group A Streptococcal infection to acute rheumatic fever (ARF) and chronic RHD. Understanding these genetic influences is essential for improving early detection and prevention strategies. Methods: A comprehensive narrative literature search was conducted using PubMed, Scopus, and Google Scholar to identify studies examining genetic susceptibility to RHD. Eligible articles included those focused on immune response genes, regional epidemiology, and genetic markers such as HLA alleles, cytokine polymorphisms, and genome-wide association study (GWAS) findings. Results: HLA class II genes-particularly HLA-DR and HLA-DQ-have shown consistent associations with RHD across African, South Asian, and Latin American populations. Cytokine gene polymorphisms, including TNF-α (-308A), IL-6 (-174G > C), and IL-10 (-1082G > A), have been linked to variations in inflammatory response and disease severity. GWAS have identified several novel loci, including the chromosome 11q21 region, which is unique to African cohorts, highlighting population-specific genetic risk. Despite Sudan's high RHD burden, no dedicated genetic studies have been conducted among Sudanese patients, leaving a substantial knowledge gap regarding local susceptibility patterns. Conclusion: Current evidence underscores the importance of genetic factors in RHD pathogenesis, yet Sudan remains significantly underrepresented in genetic research. Conducting Sudan-specific studies could identify population-specific alleles, strengthen early screening strategies, and guide tailored prevention efforts. Such work would also contribute valuable data to the broader understanding of RHD genetics across Africa.