ALDH2: Difference between revisions

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== Mutations ==

There are seven mutations observed in different ethnicities with higher relative prevalence, there is more cancer issued mutations<ref>''ALDH''2 Gene - Somatic Mutations in Cancer https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=ALDH2</ref>. Most studied of them is East Asian mutation (''ALDH''2*2) connected with alcohol flushing syndrome and other diseases<ref name="nov2020"/>. ''ALDH''2*2 alcohol flushing response is semidominant, thus heterozygotic individuals show lesser phenotype. After moderate consumption of alcohol, individuals affected by alcohol suffer from heavier hangover symptoms, homozygotes, even extreme one such as tachycardia, hypotension, nausea, and vomiting. Heterozygotes have reported subjectively more intense and more pleasant rection to alcohol than individuals with ''ALDH''2*1/2*1<ref>DOI:10.1111/j.1530-0277.1992.tb01907</ref>. There are fewer people with at least one copy of ''ALDH''2*2 who suffer from liver cirrhosis, thus is concluded that this mutation can serve as protection against excessive alcohol consumption. This fact depends on cultural differences and relationship with alcohol as the protective effect is somehow weaker in African or European populations, as there can be social pressure to drink more alcohol in social activities, even in Eastern cultures people with flushing cannot escape or reject such alcoholism<ref>DOI:10.14218/jcth.2020.00104</ref>.

There are seven mutations observed in different ethnicities with higher relative prevalence, there is more cancer issued mutations<ref>''ALDH''2 Gene - Somatic Mutations in Cancer https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=ALDH2</ref>. Most studied of them is East Asian mutation (''ALDH''2*2) connected with alcohol flushing syndrome and other diseases<ref name="nov2020"/>.

{| class="wikitable"

|-

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|-

| '''''ALDH''2*2'''

| E504K<ref>E504K https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99451499</ref>

| E504K<ref>Mutation overview page ALDH2 - p.E504K (Substitution - Missense) https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99451499</ref>

| 504

| Glu → Lys<br />

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|-

| '''''ALDH''2*4'''

| P92T<ref>P92T https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99454838</ref>

| P92T<ref>Mutation overview page ALDH2 - p.P92T (Substitution - Missense) https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99454838</ref>

| 92

| Pro → Thr

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|-

| '''''ALDH''2*5'''

| T244M<ref>T244M https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99452531</ref>

| T244M<ref>Mutation overview page ALDH2 - p.T244M (Substitution - Missense) https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99452531</ref>

| 244

| Thr → Met

Line 60:

Line 59:

|-

| '''''ALDH''2*6'''

| V304M<ref>V304M https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99451318</ref>

| V304M<ref>Mutation overview page ALDH2 - p.V304M (Substitution - Missense) https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99451318</ref>

| 304

| Val → Met

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Line 67:

|-

| '''''ALDH''2*7'''

| R338W<ref>R338W https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99455550</ref>

| R338W<ref>Mutation overview page ALDH2 - p.R338W (Substitution - Missense) https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99455550</ref>

| 338

| Arg → Trp

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| 23%

|}

== Alcohol liver disease ==

''ALDH''2*2 alcohol flushing response is semidominant, thus heterozygotic individuals show lesser phenotype. After moderate consumption of alcohol, individuals affected by alcohol suffer from heavier hangover symptoms, homozygotes, even extreme one such as tachycardia, hypotension, nausea, and vomiting. Heterozygotes have reported subjectively more intense and more pleasant rection to alcohol than individuals with ''ALDH''2*1/2*1<ref>DOI:10.1111/j.1530-0277.1992.tb01907.x</ref>. There are fewer people with at least one copy of ''ALDH''2*2 who suffer from liver cirrhosis. Therefore, is concluded that this mutation can serve as protection against alcohol abuse. This fact depends on cultural differences and relationship with alcohol as the protective effect is somehow weaker in African or European populations, as there can be social pressure to drink more alcohol in social activities, even in Eastern cultures people with flushing cannot escape or reject such alcoholism<ref name="HP">DOI:10.14218/jcth.2020.00104</ref>. Generally, individuals with the ALDH2 polymorphism experience less hepatic oxidative stress due to lesser alcohol consumption, by cumulating unprocessed acetaldehyde. Consequently, artificial regulation of ALH2 may be used as potential therapeutic intervention for alcoholism <ref>DOI:10.1073/ pnas.1908137116</ref>.

</StructureSection>

== Non-alcoholic liver diseases ==

Although ALHD2 misfunction can play a protective role against, on the other hand, it can increase the number of non-alcoholic fatty liver disease (NAFLD) among carriers of ALDH2*2. This can be the result of the missing ALDH2 enzyme for preserving mitochondrial respiratory function or for the cleavage of aldehydes, which can be byproducts of fat metabolism<ref name="HP"/>. .

There are concerns about metabolic interaction between retinol and ethanol metabolism. As I can result in inhibition of immunological feedback to some viral infections such as viral hepatitis. Among ALDH2*2 patients has increased probability of developing liver cirrhosis<ref name="HP"/>.

Hepatocellular carcinoma is suspected of connection with ALHD2 deficiency as it could be result of habitual alcohol drinking, non-alcoholic fatty liver disease or HBV. Due to the oxidative base of ethanol metabolism and the occurrence of the ALDH2 enzyme in mitochondria, is cocluded a correlation between low ALDH2 activity and liver cancer<ref name="HP"/>.

== Treatment ==

== References ==

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@@ Line 9: / Line 9: @@
 == Mutations ==
 <StructureSection load='3INL' size='350' side='right' caption='Human Mitochondrial Aldehyde Dehydrogenase Asian Variant, ALDH2*2, complexed with agonist Alda-1 (PDB entry [http://doi.org/10.2210/pdb3INL/pdb 3INL])' scene=''>
-There are seven mutations observed in different ethnicities with higher relative prevalence, there is more cancer issued mutations<ref>''ALDH''2 Gene - Somatic Mutations in Cancer https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=ALDH2</ref>. Most studied of them is East Asian mutation (''ALDH''2*2) connected with alcohol flushing syndrome and other diseases<ref name="nov2020"/>. ''ALDH''2*2 alcohol flushing response is semidominant, thus heterozygotic individuals show lesser phenotype. After moderate consumption of alcohol, individuals affected by alcohol suffer from heavier hangover symptoms, homozygotes, even extreme one such as tachycardia, hypotension, nausea, and vomiting. Heterozygotes have reported subjectively more intense and more pleasant rection to alcohol than individuals with ''ALDH''2*1/2*1<ref>DOI:10.1111/j.1530-0277.1992.tb01907</ref>. There are fewer people with at least one copy of ''ALDH''2*2 who suffer from liver cirrhosis, thus is concluded that this mutation can serve as protection against excessive alcohol consumption. This fact depends on cultural differences and relationship with alcohol as the protective effect is somehow weaker in African or European populations, as there can be social pressure to drink more alcohol in social activities, even in Eastern cultures people with flushing cannot escape or reject such alcoholism<ref>DOI:10.14218/jcth.2020.00104</ref>.
+There are seven mutations observed in different ethnicities with higher relative prevalence, there is more cancer issued mutations<ref>''ALDH''2 Gene - Somatic Mutations in Cancer https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=ALDH2</ref>. Most studied of them is East Asian mutation (''ALDH''2*2) connected with alcohol flushing syndrome and other diseases<ref name="nov2020"/>.
 {| class="wikitable"
 |-
@@ Line 29: / Line 28: @@
 |-
 | '''''ALDH''2*2'''
-| E504K<ref>E504K https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99451499</ref>
+| E504K<ref>Mutation overview page ALDH2 - p.E504K (Substitution - Missense) https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99451499</ref>
 | 504
 | Glu → Lys<br />
@@ Line 44: / Line 43: @@
 |-
 | '''''ALDH''2*4'''
-| P92T<ref>P92T https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99454838</ref>
+| P92T<ref>Mutation overview page ALDH2 - p.P92T (Substitution - Missense) https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99454838</ref>
 | 92
 | Pro → Thr
@@ Line 52: / Line 51: @@
 |-
 | '''''ALDH''2*5'''
-| T244M<ref>T244M https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99452531</ref>
+| T244M<ref>Mutation overview page ALDH2 - p.T244M (Substitution - Missense) https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99452531</ref>
 | 244
 | Thr → Met
@@ Line 60: / Line 59: @@
 |-
 | '''''ALDH''2*6'''
-| V304M<ref>V304M https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99451318</ref>
+| V304M<ref>Mutation overview page ALDH2 - p.V304M (Substitution - Missense) https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99451318</ref>
 | 304
 | Val → Met
@@ Line 68: / Line 67: @@
 |-
 | '''''ALDH''2*7'''
-| R338W<ref>R338W https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99455550</ref>
+| R338W<ref>Mutation overview page ALDH2 - p.R338W (Substitution - Missense) https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99455550</ref>
 | 338
 | Arg → Trp
@@ Line 75: / Line 74: @@
 | 23%
 |}
+== Alcohol liver disease ==
+''ALDH''2*2 alcohol flushing response is semidominant, thus heterozygotic individuals show lesser phenotype. After moderate consumption of alcohol, individuals affected by alcohol suffer from heavier hangover symptoms, homozygotes, even extreme one such as tachycardia, hypotension, nausea, and vomiting. Heterozygotes have reported subjectively more intense and more pleasant rection to alcohol than individuals with ''ALDH''2*1/2*1<ref>DOI:10.1111/j.1530-0277.1992.tb01907.x</ref>. There are fewer people with at least one copy of ''ALDH''2*2 who suffer from liver cirrhosis. Therefore, is concluded that this mutation can serve as protection against alcohol abuse. This fact depends on cultural differences and relationship with alcohol as the protective effect is somehow weaker in African or European populations, as there can be social pressure to drink more alcohol in social activities, even in Eastern cultures people with flushing cannot escape or reject such alcoholism<ref name="HP">DOI:10.14218/jcth.2020.00104</ref>. Generally, individuals with the ALDH2 polymorphism experience less hepatic oxidative stress due to lesser alcohol consumption, by cumulating unprocessed acetaldehyde. Consequently, artificial regulation of ALH2 may be used as potential therapeutic intervention for alcoholism <ref>DOI:10.1073/ pnas.1908137116</ref>.
 </StructureSection>
+== Non-alcoholic liver diseases ==
+Although ALHD2 misfunction can play a protective role against, on the other hand, it can increase the number of non-alcoholic fatty liver disease (NAFLD) among carriers of ALDH2*2. This can be the result of the missing ALDH2 enzyme for preserving mitochondrial respiratory function or for the cleavage of aldehydes, which can be byproducts of fat metabolism<ref name="HP"/>. .
+There are concerns about metabolic interaction between retinol and ethanol metabolism. As I can result in inhibition of immunological feedback to some viral infections such as viral hepatitis. Among ALDH2*2 patients has increased probability of developing liver cirrhosis<ref name="HP"/>.
+Hepatocellular carcinoma is suspected of connection with ALHD2 deficiency as it could be result of habitual alcohol drinking, non-alcoholic fatty liver disease or HBV. Due to the oxidative base of ethanol metabolism and the occurrence of the ALDH2 enzyme in mitochondria, is cocluded a correlation between low ALDH2 activity and liver cancer<ref name="HP"/>.
 == Treatment ==
 == References ==
 <references/>