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REYKJAVIK, Iceland, June 25, 2020 /PRNewswire=KYODO JBN/ --

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

Source:  deCODE Genetics Inc.