Support for the Multigenic Hypothesis of Amyloidosis: the Binding Stoichiometry of Retinol-binding Protein, Vitamin A, and Thyroid Hormone Influences Transthyretin Amyloidogenicity in Vitro

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2001 Nov 1

PMID 11687657

Citations 32

Authors

J T White

J W Kelly

Affiliations

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Abstract

The amyloidoses are a large group of protein misfolding diseases. Genetic and biochemical evidence support the hypothesis that amyloid formation from wild-type or 1 of 80 sequence variants of transthyretin causes the human amyloid diseases senile systemic amyloidosis or familial amyloid polyneuropathy, respectively. The late onset and variable penetrance of these diseases has led to their designation as multigenic--implying that the expression levels and alleles of multiple gene products influence the course of pathology. Here we show that the binding stoichiometry of three interacting molecules, retinol-binding protein, vitamin A, and L-thyroxine, notably influenced transthyretin amyloidogenicity in vitro. At least 70 genes control retinol-binding protein, vitamin A, and L-thyroxine levels in plasma and have the potential to modulate the course of senile systemic amyloidosis or familial amyloid polyneuropathy.

Citing Articles

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