Uneven burden of cardiac amyloidosis in people of African descent

Last Updated on January 1, 2025 by Joseph Gut – thasso

December 30, 2024 – Transthyretin cardiac amyloidosis (TTR-CA) is now increasingly becoming recognized as an important cause of heart failure, and some studies have shown that as much as a third of diastolic heart failure could be attributed to TTR-CA. Black populations are particularly at risk for TTR-CA as the most common form of the disease (hereditary TTR-CA) has a genetic  basis and the gene responsible is most prevalent among people with West African ancestry. This perspective piece explores the challenges that individuals of African and Caribbean populations face when confronted with the burden of TTR-CA. Key issues include the absence of rigorous disease registries, deficits in human resources, a lack of infrastructure for testing and treatment, poor awareness and health literacy, financial limitations including an inadequate public health budget, and the absence of social safety nets. To address these challenges, proactive strategies are needed to build infrastructure and local capacity which will provide the framework for an effective response. Interventions should include healthcare financing mechanisms to protect and care for vulnerable and at-risk populations with a long-term strategy of increasing the financial remuneration for health workers in developing countries to prevent the brain drain. Additionally, pharmaceutical companies need to play an active role in promoting inclusive access and global health equity in the access to the new treatments for TTR-CA which predominantly affects Black populations. Collaborative ventures with international centers of excellence can help improve access in these communities, leveraging their expertise and resources.

While it can affect individuals of any ethnic background, there is growing evidence that people of African descent are disproportionately affected by cardiac amyloidosis, particularly transthyretin cardiac amyloidosis (TTR-CA). This condition has a significant impact on the affected individuals and their communities, leading to reduced quality of life, increased morbidity and mortality rates, and a higher burden on healthcare systems. Understanding the unique characteristics and challenges of TTR-CA in individuals of African descent is crucial for developing targeted interventions and improving outcomes in these populations.

A genetic basis for cardiac amyloidosis was first suggested by the Los Angeles County study where investigators reviewed 52,370 autopsies and found that the prevalence of cardiac amyloidosis among African-Americans (1.6%) was significantly greater than the prevalence among White Americans (0.42%), even though all other types of amyloidosis were less prevalent among African-Americans. Eventually, more than 150 point mutations of the transthyretin gene (TTR gene) have been discovered. The most common mutation results from a

G to A transition at a CG dinucleotide in codon 142 (122 of the mature protein) which causes an isoleucine substitution for valine (V142I). This mutation is almost exclusively found in people of African descent. Cohort studies in the USA have shown that 3–4% of self-identified African-Americans carry this gene variant (allele frequency 0.02), and it is rare in people of other ethnicities. The only genetic study in Africa has shown that this variant allele is most prevalent (allele frequency 0.0253, about 5% of the population) in the contiguous West African countries of Sierra Leone, Guinea, Ivory Coast, Burkina Faso, Ghana, and Nigeria.

Note also that iIncreased genetic susceptibility in people of African decent  for a variety of traits have already been the theme of several posts by thasso, such as in “new trait loci for hypertension“, “mutations in colorectal cancers“, “new type 2 diabetes risk locus“, or “African ancestry linked to worse CRC outcomes“, just to name a few.

See here a sequence on TTR-CA in pepople of African decent:

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