Sci Adv: First Discovery . . People who drink and blush are more likely to develop anaemia/mental retardation/dwarfism

Aldehyde dehydrogenase 2 (ALDH2) detoxifyes acetaldehyde into acetics, but is inactivated in about 50% of the population of East Asian countries due to functional mononucleotide polymorphism rs671 (ALDH2 x 2, c.1510G-A, p.E504K).
known to have the Rs671 mutation, drinking alcohol causes an "alcohol redness reaction."
detoxify endogenous aldehyde, the main source of DNA damage repaired by fanconi's anemia pathway.
December 18, 2020, Yasuyoshi Oka of Nagoya University in Japan and others published an online report in Science Advances entitled "Digenic mutations in ALDH2 and ADH5 Impaired formaldehyde clearance and cause a multisystem disorder, AMeD syndrome"s research paper, which found that the rs671 defect allied gene and the ethanol dehydrogenase 5 (ADH5) gene combined mutation, leading to the previously unknown disease AMeD (regenerative anemia, mental retardation and dwarfism) syndrome.
cell studies have shown that reduced formaldehyde tolerance is the basis for hematopoietic stem cell differentiation and loss of proliferation capacity.
addition, Adh5-/-Aldh2E506K /E506K dual defect mice summarized key clinical characteristics of AMeDS, showing short life, dwarfism and hemagnetic failure.
, the results show that the DNA damage caused by aldehyde base is overloaded, which leads to saturation of the DNA repair process, and the comprehensive defect of aldehyde purge mechanism leads to complex clinical characteristics.
, such as acetaldehyde and formaldehyde, are cytoxic and carcinogenic because they destroy DNA and interfere with transcription and replication.
Acetaldehyde is mainly produced by oxidation and degradation of alcohol intake, while formaldehyde is a common carbon (1C) metabolite, which is produced through a variety of biochemical reactions in the body, including histones and nucleic acids of enzyme-driven demethylation.
these free aldehydes are rapidly oxidized by cell dehydrogenase into harmless carcogenic acid.
dehydrogenase 2 (ALDH2) detoxifyes acetaldehyde into acetic salts, but is inactivated in about 50% of the population of East Asian countries due to functional mononucleotide polymorphism rs671 (ALDH2 x 2, c.1510G-Gt;A, p.E504K).
known to have the Rs671 mutation, drinking alcohol causes an "alcohol redness reaction."
clearly, redness is not a disease.
, however, the rs671 defect (A) allegen prevents alcoholism and also increases the risk of a variety of clinical conditions, including cardiovascular disease and certain types of cancer.
, the incidence of gastrointestinal cancer, represented by esophageal squamous cell carcinoma, was higher when individuals with rs671 defective allegens regularly drank alcohol.
although there are many known genetic associations, genetic diseases caused by rs671 have not been reported.
Regarding the removal of formaldehyde, ethanol dehydrogenase 5 (also known as formaldehyde dehydrogenase or S-nitro glutathione reductase, ADH5 / FDH / GSNOR) is the main enzyme that converts formaldehyde into formaldehyde in a glutathione-dependent manner.
ADH5 polymorphism is known to be associated with an increased risk of cardiovascular disease because it is also a key enzyme that regulates the conduction of cell nitric oxide signals, thereby regulating circulatory function.
, however, no congenital diseases due to the loss of ADH5 function have been reported so far.
when the metabolic process of aldehyde removal becomes unstoppable, various types of endogeneic DNA damage increase.
mainly produces DNA interceding (ICL) and non-enzyme DNA-protein crosslinking (DPC).
dna damage prevents the development of replication forks.
As a result, they are thought to be largely repaired by replicating conceded DNA repair mechanisms such as (i) the ICL repair pathway involves the "FANC" protein, which mutates in Fanconi anemia (FA), a rare genetic bone marrow failure syndrome (IBMFS), which is activated in stage S and is linked to structurally specific kernelase. The Watson/Crick chain eliminates the ICL and is followed by a repair process involving cross-pathological synthesis (TLS), congenital recombination and nucleotide removal (NER);
mutations in the SPRTN gene can also cause rare diseases, Ruijs-Aalfs syndrome (RJALS), which is characterized by segmented premature aging and premature hepatocellular carcinoma.
in this study, many families with new forms of IBM FS cases were reported.
based on genomic analysis of patients, the study identified disease-causing twin mutations in the ALDH2 and ADH5 genes.
and animal studies have shown that simultaneous loss of ALDH2 and ADH5 activity can lead to increased cell formaldehyde sensitivity and multiple system abnormalities, including hematogenic failure.
results suggest that formaldehyde removal is as important as normal-developing DNA repair systems in humans and mice.
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