Disentangling Knots of Misfolded Proteins: Do We Really Know the Prognostic Implications of the Pathogenic V122I TTR Variant?

The valine to isoleucine replacement at position 122 (V122I) of the transthyretin (TTR) protein destabilizes its tertiary structure and is the rate-limiting step towards TTR amyloidogenesis. This variant is virtually exclusive to those of African ancestry with a carrier frequency of ∼3-4% (1) and is the most common cause of hereditary transthyretin cardiac amyloidosis (ATTR-CA) in the world (1, 2). However, because the vast majority of individuals with V122I TTR variant ATTR cardiac amyloidosis (V122I ATTRv) are Black, a population with disparately worse heart failure outcome s than white individuals, more clarity is needed to establish whether this genotype causes a more aggressive form of amyloidosis compared with other TTR genotypes.
Source: The American Journal of Cardiology - Category: Cardiology Authors: Tags: Editorial Source Type: research