Collaborative Research Center

The RHDGen Network: Genetics of rheumatic heart disease and molecular epidemiology of Streptococcus pyogenes pharyngitis

Project Leads

Prof Bongani Mayosi

University of Cape Town

Prof Mark Engel

University of Cape Town

The Problem

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Rheumatic heart disease (RHD) results from a harmful response of the immune system to a bacterium called Streptococcus pyogenes or Group A Streptococcus (GAS). Although the development of RHD can be prevented by the treatment of GAS infection with penicillin, this has not been successful in poor countries of Africa. The project aims to read the genome of 2,500 people with RHD and compare with 3,500 people without RHD to identify genetic risk factors. It is likely that genetic studies may identify people at high risk for the development of RHD who may be prioritised for preventive treatment and vaccination.

Project Strategy

  1. To recruit 2,500 patients with echocardiographically-confirmed RHD.
  2. To conduct a case-control genome-wide association study by genotyping 5 million single nucleotide polymorphisms in 1,500 RHD cases and 1,500 unrelated controls using micro-array technology, followed by replication in a further 1,000 independent cases and 2,000 family-based controls, and combined analysis of genotype data from all 2,500 cases and 2,500 controls or pseudo-controls to detect rarer alleles or alleles of smaller effect.
  3. To train 16 scientists and clinicians in genomic studies of multifactorial disease and ethical, legal, and social issues (ELSI) that are relevant to Africa. This will be at masters, doctoral and postdoctoral levels

Potential Impact

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A new study titled “Association of Novel Locus with Rheumatic Heart Disease in Black African Individuals” was published in the online medical publication JAMA Network in 2021. The study, which was written by a team of researchers within the RHDGen Network revealed a novel candidate susceptibility locus that is exclusive to Black African individuals and is an important heritable component to rheumatic heart disease (RHD) susceptibility in Black Africans. Tafadzwa Machipisa, a doctoral student based in the Department of Medicine at the University of Cape Town and the lead author on the paper indicated that their findings may provide insight as to why RHD is even more common in Black Africans than in previously studied populations. The results will further allow interstudy analyses to get the bigger picture on a global population scale, to find global solutions to the RHD epidemic. The study concludes that understanding