The effects and tolerance of alcohol vary greatly from person to person. This difference is largely due to genetics, with specific genes involved in the rate at which alcohol is broken down in the body and the metabolic pathways involved. Recent research has revealed the genetic factors involved in alcohol tolerance. In this article, we will take a closer look at the mechanisms of genes involved in alcohol metabolism and their impact on health and drinking habits.
Alcohol metabolism and genetics
After ingestion, alcohol is broken down in the body and then excreted. The two main enzymes involved in this process are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Differences in the genes that code for these enzymes affect the ability to break down alcohol.
1. ADH gene (alcohol dehydrogenase)
The ADH gene codes for an enzyme that breaks down alcohol into acetaldehyde . High ADH activity leads to faster alcohol breakdown.
People with ADH1B*2 mutation : Alcohol is broken down quickly, and blood acetaldehyde levels rise rapidly. The face tends to turn red (flushing reaction).
People with ADH1B*1 blood type : Alcohol is broken down slowly, and alcohol tends to remain in the blood for a long time.
2. ALDH2 gene (aldehyde dehydrogenase)
The ALDH2 gene encodes an enzyme that breaks down acetaldehyde into harmless acetic acid. Mutations in this gene reduce the ability to break down acetaldehyde, making people more susceptible to hangovers and nausea.
People with the ALDH2*2 mutation (reduced activity) : Acetaldehyde is prone to accumulate in the body, and they are prone to experiencing facial redness, palpitations, and nausea after drinking alcohol.
People with ALDH2*1 type (normal active type) : The breakdown of acetaldehyde is smooth, and they are less likely to become ill even if they consume alcohol.
Genetic influences also play a role in the differences in drinking habits between people with low and high alcohol breakdown abilities.
1. Alcoholism and genetic factors
It has become clear that genetic factors are strongly involved in alcoholism. In particular, it has been found that the GABRA2 gene and CHRM2 gene are involved in the risk of alcohol dependence.
People with GABRA2 gene mutations: They are more likely to feel the rewarding effects of alcohol and are more likely to drink repeatedly.
People with CHRM2 gene mutations: They are more susceptible to the effects of stress relief through alcohol and are at higher risk of alcohol dependence.
The CYP2E1 gene is involved in the metabolism of alcohol in the liver, and mutations in this gene increase the risk of alcohol-induced liver damage.
People with CYP2E1 mutations : Alcohol-induced damage to liver cells is more likely to progress, and they are at higher risk of alcoholic hepatitis.
People without the mutation : Alcohol metabolism is relatively stable and has little effect on liver function.
Reference research:
CYP2E1遺伝子と肝臓疾患
2. Cancer risk (ADH1C gene)
The ADH1C gene affects the rate at which alcohol is metabolized and alters the risk of alcohol-related cancer, particularly in the areas of esophageal and liver cancer.
People with ADH1C mutations : Alcohol metabolism is slower, which leads to prolonged accumulation of acetaldehyde, increasing the risk of cancer.
People without the mutation : Metabolize alcohol quickly and are at lower risk.
Further analysis of alcohol effects using genetic information
The effects of alcohol are not simply determined by the rate at which it is broken down, but also by differences in brain response, immune system, and even metabolism. By analyzing genetic information in detail, it is possible to more accurately understand the effects of alcohol on the body and take appropriate measures.
1. Alcohol and the brain’s response: genetic influences
When we consume alcohol, the neurotransmitters in the brain change, making us feel relaxed and euphoric. However, this varies from person to person and is thought to be related to genetic differences.
DRD2 gene and dopamine function
The DRD2 gene encodes a dopamine receptor and is involved in the pleasure felt by alcohol users and the risk of dependence.
People with the DRD2 A1 mutation : They have fewer dopamine receptors and feel the rewarding effects of alcohol more strongly, so they are more likely to drink more alcohol.
People with DRD2 A2 blood type : Their dopamine receptors are normally active and they are less susceptible to the effects of alcohol.
The OPRM1 gene and endorphin response
The OPRM1 gene encodes a receptor for endorphins (drugs produced in the brain) and influences the mood-enhancing effects of alcohol consumption.
People with OPRM1 mutations : They experience a strong sense of euphoria when consuming alcohol and are prone to dependence.
People with normal OPRM1 : They do not feel the effects of alcohol as strongly, making it easier to control their drinking.
2. Alcohol and the immune system: genetic influences
Alcohol also affects the immune system, making you more susceptible to inflammatory responses over time. Your susceptibility to this effect is partly determined by your genes.
IL6 gene and inflammatory response
The IL6 gene controls the production of inflammatory cytokines and regulates immune function.
People with high IL6 activity: Alcohol consumption is likely to cause excessive inflammatory responses, increasing the risk of liver and digestive system diseases.
People with low IL6 activity: are less susceptible to the inflammation caused by alcohol.
3. Alcohol and metabolism: genetic influences
Alcohol is high in calories and can lead to fat storage depending on how much you consume, and your genes determine how efficiently you metabolize it.
The PPARGC1A gene and fat metabolism
The PPARGC1A gene plays a role in regulating energy metabolism and fat burning.
People with high PPARGC1A activity : They can burn alcohol calories as energy efficiently and are less likely to store them as fat.
People with low PPARGC1A activity : Calories burned after alcohol consumption are slower and are more likely to be stored as fat.
4. Measures against alcohol use using genetic information
By utilizing genetic testing, it is possible to correctly understand one’s alcohol tolerance and risks and take appropriate measures.
1. Genotype-specific drinking guidelines
Gene
Influence
Recommendations
ADH1B*2 mutation
Alcohol decomposition is fast, but acetaldehyde accumulates
Drink less alcohol and more water
ALDH2*2 mutation
The breakdown of acetaldehyde is slow, making you more susceptible to hangovers
Drink only small amounts of alcohol
CYP2E1 mutations
Risk of liver dysfunction
Eat foods that protect the liver (turmeric, green tea)
DRD2 mutations
Feeling strong pleasure from drinking alcohol
Be conscious of your drinking habits and manage them
2. Gene-based personalized alcohol strategy
People with low ALDH2 activity : Choose non-alcoholic or low-alcohol drinks.
People with CYP2E1 mutations : Eat more antioxidant foods to protect liver function.
People with the GABRA2 mutation : Alternatives to alcohol include exercise and relaxation.
Further analysis of alcohol effects using genetic information
The effects of alcohol go beyond just differences in the rate at which it is broken down, and are related to the liver, nervous system, cardiovascular system, and even long-term health risks. By analyzing genetic information in detail, we can accurately understand each individual’s risk and take appropriate measures.
1. Genetic effects of alcohol on the cardiovascular system
Alcohol consumption is known to affect blood pressure and vascular health, and certain genetic differences make some people more susceptible to the effects of alcohol than others.
ACE gene and blood pressure
The ACE (angiotensin-converting enzyme) gene is involved in regulating blood pressure. Mutations in this gene make people more susceptible to the effects of alcohol on blood pressure.
People with ACE type I/I: Alcohol intake is less likely to increase blood pressure.
People with PNPLA3 G/G genotype: Alcohol intake is likely to cause fat accumulation in the liver, increasing the risk of cirrhosis.
2. Genetic risk for alcohol and liver disease
Long-term alcohol consumption increases the risk of liver diseases such as fatty liver and cirrhosis. Certain genes play a role in susceptibility to liver damage.
PNPLA3 gene and fatty liver
The PNPLA3 gene plays a role in regulating lipid metabolism in the liver, and mutations in this gene increase the risk of fatty liver caused by alcohol consumption.
People with PNPLA3 I/I genotype: Low risk of fatty liver due to alcohol consumption.
People with PNPLA3 G/G genotype: Alcohol intake is likely to cause fat accumulation in the liver, increasing the risk of cirrhosis.
3. Alcohol and sleep: genetic influences
Alcohol is known to induce temporary drowsiness, but also to reduce the quality of sleep. This effect varies from person to person depending on genetic factors.
PER3 gene and sleep quality
The PER3 gene regulates the body’s circadian rhythm and determines how susceptible a person is to the effects of alcohol.
People with long PER3 variants: Less alcohol-induced impairment of sleep quality.
People with short PER3 variants: Alcohol intake reduces deep sleep and increases nighttime awakenings.
4. Alcohol and metabolism: genetic influences
Individuals metabolize alcohol at different rates, which affects them differently.
The FTO gene and alcohol-induced weight gain
The FTO gene is involved in appetite and energy expenditure and is one of the genes that are susceptible to the effects of alcohol.
People with the FTO mutation are more likely to experience weight gain from alcohol consumption.
People with normal FTO : Alcohol intake has less effect on their metabolism.
Further analysis of alcohol effects using genetic information
Alcohol affects not only metabolism and the liver, but also the nervous system, bone health, and even the intestinal environment. Recent research has revealed that these effects are determined by genes. Detailed analysis of genetic information can accurately identify individual risks and establish appropriate drinking habits.
1. Alcohol and the nervous system: the role of genes
Alcohol affects neurotransmitters in the brain, resulting in a short-term mood boost and relaxation, but in the long term it can decrease brain function and increase the risk of dementia.
The BDNF gene and neuronal health
The BDNF (brain-derived neurotrophic factor) gene plays a role in promoting the growth and repair of nerve cells. People who are susceptible to the effects of alcohol often have reduced activity of this gene.
People with low BDNF activity : These people are more likely to suffer from increased damage to nerve cells caused by alcohol, and are more likely to experience declines in memory and concentration.
People with high BDNF activity : They have a high ability to repair nerve cells and are less susceptible to the effects of alcohol.
2. Alcohol and bone health: genetic influences
Alcohol also affects bone density, and it is known that long-term excessive alcohol consumption increases the risk of osteoporosis. Genetics plays a role in whether or not you are susceptible to this effect.
COL1A1 gene and bone mineral density
The COL1A1 gene regulates the production of collagen, a major component of bone, and mutations in this gene may increase the risk of bone mineral density loss due to alcohol consumption.
People with the COL1A1 mutation : Alcohol consumption slows bone formation, making bones more susceptible to fractures.
People without the mutation : Less affected by alcohol and easier to maintain bone density.
3. The relationship between alcohol and intestinal environment: influence of genes
Alcohol has been reported to disrupt the balance of gut bacteria and affect digestive health, and it has been shown that alcohol affects the intestines differently depending on certain genes.
FUT2 gene and intestinal flora
The FUT2 gene is involved in the establishment of good bacteria in the intestines, and mutations in this gene make the intestinal environment more susceptible to the effects of alcohol.
People with the FUT2 mutation : Alcohol consumption reduces the good bacteria in the intestines, making them more susceptible to indigestion and inflammation.
People with normal FUT2 : There are fewer changes to intestinal bacteria caused by alcohol, making it easier to maintain digestive health.
4. Alcohol and longevity: genetic influences
The relationship between alcohol consumption and longevity may also have a genetic component.
The SIRT1 gene and aging
The SIRT1 gene works to suppress cellular aging and may reduce the effects of alcohol.
People with high SIRT1 activity : They suffer less cell damage from alcohol consumption and tend to live longer.
People with low SIRT1 activity : Alcohol can accelerate cellular aging, increasing the risk of lifestyle-related diseases.
The relationship between alcohol decomposition ability and genes
When alcohol enters the body, it is first metabolized in the liver. This metabolic process involves the enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), and the strength of the effects of alcohol is determined by the activity of these enzymes.
Alcohol dehydrogenase (ADH) and its genetic differences
ADH is an enzyme that breaks down alcohol into acetaldehyde, and there are genetic differences in the activity of this enzyme. If ADH activity is strong, alcohol is broken down quickly and acetaldehyde accumulates rapidly, causing a flushing reaction (redness in the face). On the other hand, if ADH activity is weak, alcohol remains in the body for a long time and people become intoxicated easily.
Differences and effects of aldehyde dehydrogenase (ALDH)
ALDH is an enzyme that converts acetaldehyde into harmless acetic acid, and when the activity of this enzyme is low, acetaldehyde accumulates in the body, causing hangovers, palpitations, and nausea. Genetic differences in ALDH clearly distinguish between people who can tolerate alcohol and those who can tolerate alcohol.
People with low ALDH activity are prone to feeling unwell even with small amounts of alcohol, so forcing themselves to continue drinking can increase their health risks.
Alcohol’s effects on the brain and the role of genes
Alcohol also affects neurotransmitters in the brain, which can make you feel relaxed or euphoric, but genetic differences play a role in how susceptible people are to these effects.
Dopamine receptors and the rewarding effects of alcohol
When we consume alcohol, it promotes the secretion of dopamine in the brain, which gives us a sense of pleasure. However, the number and sensitivity of dopamine receptors vary genetically, and some people are more likely to feel the pleasure of alcohol than others.
People with high dopamine receptor sensitivity tend to feel the rewarding effect of alcohol more strongly and are more likely to develop a drinking habit. Conversely, people with low dopamine receptor sensitivity do not feel the pleasure of alcohol as much and are therefore less likely to develop a drinking habit.
Serotonin and the stress-relieving effects of alcohol
Alcohol has a temporary stress-relieving effect, which is related to the secretion of a neurotransmitter called serotonin. People with high serotonin activity are less likely to feel the stress-relieving effect of alcohol and tend to drink less. On the other hand, people with low serotonin secretion are more likely to be relaxed by alcohol and are at higher risk of addiction.
Alcohol puts a strain on the liver, and long-term drinking increases the risk of liver damage, but susceptibility to this effect also varies by gene.
Genetic risk of alcoholic fatty liver disease
Alcohol consumption can increase the accumulation of fat in the liver, which can lead to fatty liver disease. People with certain genetic mutations are more susceptible to alcohol-induced fat accumulation and are at higher risk of fatty liver disease.
People with this type are advised to limit alcohol intake and actively consume a diet that promotes fat burning in the liver (fish, nuts, and green and yellow vegetables containing omega-3 fatty acids).
Differences between cirrhosis risk and genes
Long-term alcohol consumption destroys liver cells and increases the risk of cirrhosis. Whether or not you are susceptible to this depends on the genes that control the liver’s detoxification function.
If you have a genetic type that puts you at high risk for cirrhosis, it’s important to limit your alcohol intake and include foods that support liver function (such as turmeric, lemon, and green tea).
Alcohol and the cardiovascular system: genetic factors play a role
Alcohol has the effect of dilating blood vessels and temporarily promoting blood flow. However, it is known that people who are genetically at high risk for high blood pressure and arteriosclerosis are more susceptible to the effects of alcohol and are more likely to experience an increase in blood pressure.
Characteristics of gene types with high risk of elevated blood pressure
Mutations in genes that regulate blood pressure make people more susceptible to the effects of alcohol intake on blood pressure. People with genetic types that are at high risk of high blood pressure are advised to limit alcohol intake and adopt low-salt diets and exercise habits.
The relationship between alcohol and heart disease risk
Excessive alcohol intake also puts a strain on the cardiovascular system and increases the risk of cardiomyopathy and arteriosclerosis. People who are genetically at high risk for cardiovascular disease can benefit by properly managing their alcohol intake and adopting a heart-healthy diet (Mediterranean diet).
Optimizing alcohol management using genetic information
By utilizing genetic information, it is possible to establish a drinking style that suits your constitution and minimize health risks. By undergoing appropriate genetic testing, you can gain a deeper understanding of the effects of alcohol and practice evidence-based health management.
How to use genetic information to appropriately interact with alcohol
By understanding your own alcohol tolerance and health risks based on your genetic information, you can develop more appropriate drinking habits.
1. Measures for people with slow alcohol metabolism
Drink plenty of fluids before drinking to support your metabolism.
Take a day off from drinking to prevent the accumulation of acetaldehyde.
Include foods containing B vitamins (liver, nuts) to help support the liver’s detoxification function.
2. Measures for people who are susceptible to the stress-relieving effects of alcohol
Instead of relying on alcohol, try to find other ways to relieve stress, such as exercise or a hobby.
Be mindful of drinking in moderation to reduce the risk of addiction.
3. Measures for people who are susceptible to liver damage
Reduce your alcohol intake and actively consume foods that protect your liver (turmeric, green tea).
Have regular liver function tests to detect abnormalities early.
By understanding your genetic characteristics and managing your drinking accordingly, you can enjoy alcohol while maintaining your health.
By utilizing genetic information, it is possible to understand the effects and tolerance of alcohol on an individual basis and establish appropriate drinking habits. The rate at which alcohol is metabolized, the burden on the nervous system and liver, and the risk of alcohol dependence are all determined by genetics, so it is important to understand one’s own constitution.
By managing your drinking properly, you can enjoy alcohol while minimizing health risks. By utilizing genetic testing and practicing evidence-based drinking habits, you can achieve a healthier lifestyle.
