REYKJAVIK, Iceland,
June 24, 2020 /PRNewswire/ --
Scientists at deCODE genetics, a subsidiary of Amgen, and
their collaborators from the Icelandic healthcare system,
University of Iceland and the
Karolinska Institute in Sweden, today publish a study in
Nature, comparing over 30 thousand patients with autoimmune
thyroid disease from Iceland and
UK with 725 thousand controls. Autoimmune thyroid disease (AITD) is
the most common autoimmune disease and is highly heritable. The
scientists found 99 sequence variants that associate with
autoimmune thyroid disease and 84 of those had not been associated
with the disease before.
One of the newly discovered sequence variants is in a gene that
codes for the FLT3 receptor (fms-related tyrosine kinase 3) on
blood cells and immune cells, and is of large interest for several
reasons.
First, it strongly increases the risk of autoimmune thyroid
disease and other autoimmune diseases, both systemic lupus
erythematosus (SLE), rheumatoid arthritis (RA) and celiac disease.
These diseases are all characterized by autoantibodies and are
more common in women than men. Furthermore, patients with
these diseases are quite often affected by autoimmune thyroid
disease as well.
Second, it is known that activating somatic mutations in the
FLT3 gene associate with acute myeloid leukemia (AML).
Therefore, the scientists tested whether this FLT3 germline
variant, affects the risk of AML like it increases the risk of
autoimmune diseases. It turned out that it almost doubles the risk
of AML, but not the risk of cancer overall.
Third, it is quite remarkable that this variant in FLT3,
which is in an intron of the gene and does not directly affect
coding sequence, can have so strong effect on disease risk. It
turns out that the variant introduces a stop codon in one-third of
the transcripts, which results in a shorter protein that lacks the
kinase part, which is essential for its function.
Finally, this variant in FLT3 affects the plasma
levels of several other proteins in the body, especially the
ligand of FLT3, resulting in almost double the level in carriers.
This molecular couple, the FLT3 receptor and its ligand, has a key
role in the development of blood cells that are important in both
acute myeloid leukemia and immune responses. Hence, this variant is
a loss of function mutation that through compensatory increase in
the level of the ligand, acts as a gain of function.
"This report describes a novel major risk gene for several
autoimmune diseases, discovered through a genome-wide study on
autoimmune thyroid disease, and how the risk variant affects the
gene product, FLT3, and consequently the level of the ligand to the
FLT3 receptor in blood, thereby demonstrating its functional
importance," says Prof. Saedis Saevarsdottir,
scientist at deCODE genetics and first author
on the paper
"The discoveries presented in this paper are based on the
sequential application of genomics, transcriptomics and proteomics;
the combination of these three omics in a hypothesis independent
manner yields a remarkably powerful approach to the study of human
disease," says Kari Stefansson,
CEO of deCODE genetics and senior author on the paper.
Based in Reykjavik, Iceland,
deCODE is a global leader in analyzing and understanding the human
genome. Using its unique expertise in human genetics combined with
growing expertise in transcriptomics and population proteomics and
vast amount of phenotypic data, deCODE has discovered risk factors
for dozens of common diseases and provided key insights into their
pathogenesis. The purpose of understanding the genetics of disease
is to use that information to create new means of diagnosing,
treating and preventing disease. deCODE is a wholly-owned
subsidiary of Amgen (NASDAQ: AMGN).
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Contact:
Thora Kristin Asgeirsdottir
PR and Communications
deCODE genetics
thoraa@decode.is
+354 894 1909
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SOURCE deCODE genetics Inc.