“People of Asian ancestry cannot metabolize alcohol.”

The point mutation in aldehyde dehydrogenase 2 (ALDH2), identified as ALDH2*2, is the most frequent variant in humans and is present in 8% of the world’s population, or approximately 560 million people. … For heterozygous ALDH2*1/*2 individuals, the possible combinations reduce overall ALDH2 enzymatic activity by 60% to 80% compared to those of wild-type homozygous ALDH2*1/*1 individuals.

Based on the characteristics of the 1212 isozyme, it would be expected that Asians who have this isozyme would metabolize ethanol at a greater rate than persons without the isozyme. … However, about 50 percent of the Asian subjects tested did not have the active ALDH2 isozyme. Further work on sub jects deficient in the active ALDH2 isozyme has shown that the enzyme is present, but not in the active form.

The alcohol flush reaction is a type of alcohol intolerance—not an “alcohol allergy”—and is a condition predominantly due to inherited variations in genes of certain enzymes, causing people to metabolize alcohol less efficiently. … Variations in the alcohol dehydrogenase gene, ADH1B, and the aldehyde dehydrogenase gene, ALDH2, are well-known variations that lead to higher acetaldehyde levels due to altered alcohol metabolism and are more common among people of East Asian ancestry.

These genes encode enzymes that metabolize alcohol into acetaldehyde (ADH1B) and acetaldehyde into acetate (ALDH2). Genetic variants in ALDH2 and ADH1B alter alcohol metabolism leading to prolonged, elevated levels of acetaldehyde.

A relatively large subset of this population carries a unique loss-of-function point mutation in aldehyde dehydrogenase 2 (ALDH2), ALDH2*2. Found in approximately 560 million people of East Asian descent, ALDH2*2 reduces enzymatic activity by approximately 60% to 80% in heterozygotes.

Approximately 36% of East Asians (560 million) or nearly 8% of the global population, carry an inactivating Glu504Lys missense mutation of the ALDH2 gene3. This mutation results in a reduction of the ALDH2 enzymatic activity by 60–80% in heterozygous carriers and ~90% in homozygous carriers4. People carrying this mutation exhibit sensitivity to alcohol, with presentations ranging from facial flushing, headache, and tachycardia due to a rapid increase in circulating acetaldehyde concentrations5,6.

An isozyme of ADH (beta 2 beta 2) is found more frequently in Asians than in whites, and an ALDH isozyme (ALDH2), although present in Asians, often is in an inactive form. … The presence of an inactive form of ALDH2 is thought to be responsible for an increase in acetaldehyde levels in the body. … Although the presence of an inactive ALDH2 isozyme may serve as a deterrent to alcohol consumption, its presence does not fully explain the levels of alcohol consumption by those with the inactive isozyme.

Approximately 36% of East Asians (Japanese, Chinese, and Koreans) show a characteristic physiological response to drinking alcohol that includes facial flushing (see Figure 1), nausea, and tachycardia [1] . This so-called alcohol flushing response (also known as “Asian flush” or “Asian glow”) is predominantly due to an inherited deficiency in the enzyme aldehyde dehydrogenase 2 (ALDH2) [2]. … Alcohol consumed by ALDH2-deficient individuals is metabolized to acetaldehyde, which accumulates in the body due to absent ALDH2 activity and results in facial flushing (Figure 1), nausea, and tachycardia [2]. … ALDH2 Lys/Glu heterozygotes experience a less severe manifestation of the flushing response due to residual but low ALDH2 enzyme activity in their cells.

Consistent with this assumption, in vitro and in vivo studies have demonstrated that compared with the enzyme activity generated in cells or organisms homozygous for ALDH2*1 (i.e., ALDH2*1/*1 genotype), those who are heterozygous show only 12 to 20 percent of the enzyme activity and elevated acetaldehyde levels, and those who are homozygous for ALDH2*2 show no enzyme activity and even higher acetaldehyde levels (Bosron and Li 1986; Wall et al. 1997b ).

The ALDH2 Glu504Lys mutant allele has a high-frequency distribution in East Asian populations and has been demonstrated to be associated with an increased risk of cardiovascular disease, stroke, and tumors. … The frequency of this variant of ALDH2 (ALDH2 Glu504Lys) is low in caucasian, whereas the frequency is 30-50% in East Asian populations, especially in Chinese, Korean and Japanese (Goedde et al. 1992 ).

Nearly all people of Caucasian and African-American descent are homozygous for the functional ALDH21 allele. Among Asians, however, only about 50 percent are homozygous for ALDH21, 30 to 40 percent are heterozygous, and 5 to 10 percent are homozygous for the defective ALDH22 allele.

After ingesting 0.3 g/kg of alcohol, blood ethanol, acetaldehyde, and acetate concentrations, as well as the facial skin blood flow (FSBF) and pulse rate were measured for 130 min.

Approximately 36% of East Asians (560 million) or nearly 8% of the global population, carry an inactivating Glu504Lys missense mutation of the ALDH2 gene 3. This mutation results in a reduction of the ALDH2 enzymatic activity by 60–80% in heterozygous carriers and ~90% in homozygous carriers 4. People carrying this mutation exhibit sensitivity to alcohol, with presentations ranging from facial flushing, headache, and tachycardia due to a rapid increase in circulating acetaldehyde concentrations 5, 6.

Current alcohol flushing, the inactive ALDH2*1/*2 genotype, and the fast-metabolizing ADH1B*2 allele were less frequently found in the AD groups.

One of these gene variants, which generates a nonfunctional enzyme, is present in Asians but not in Caucasians and African-Americans. … People with two copies of the defective gene respond to alcohol consumption with intense flushing and other unpleasant reactions, such as nausea. … People with one copy of the defective gene also flush after ingesting alcohol and are at relatively lower risk for alcoholism than people with fully functional genes.

As described in this comic, the facial flushing that occurs after alcohol consumption is a warning sign that the body cannot break-down a metabolite of alcohol, called acetaldehyde. … Since alcohol is typically a beverage we drink, the alcohol exposure is concentrated within the digestive system -leading to higher risks of cancer particularly of the upper digestive track (mouth and esophagus) due to the limited ability to metabolize the alcohol metabolite acetaldehyde to acetic acid.

As described in this comic, the facial flushing that occurs after alcohol consumption is a warning sign that the body cannot break-down a metabolite of alcohol, called acetaldehyde. … Since alcohol is typically a beverage we drink, the alcohol exposure is concentrated within the digestive system -leading to higher risks of cancer particularly of the upper digestive track (mouth and esophagus) due to the limited ability to metabolize the alcohol metabolite acetaldehyde to acetic acid.

The inactive aldehyde dehydrogenase 2 (*ALDH2*) and highly active alcohol dehydrogenase-1B (*ADH1B*) genes are protective factors for the development of AUD. … The inactive*ALDH2*provides its protective effect through the accumulation of acetaldehyde after consuming alcohol, resulting in unpleasant effects, and heightened sensitivity to alcohol.

The ALDH2*2 missense variant that commonly causes alcohol flushing reactions is the single genetic polymorphism associated with the largest number of traits in humans. The dysfunctional ALDH2 variant affects nearly 8% of the world population and is highly concentrated among East Asians. … Many heterozygous ALDH2 variant carriers have developed tolerance to the acetaldehyde-induced flushing response and become habitual heavy drinkers. The number of alcoholics or heavy drinkers (consuming >400 g of ethanol per week) with the heterozygous ALDH2*2 genotype has risen rapidly in the past few decades among East Asians from 2-3% to 17-26% in Japan and Taiwan (Higuchi et al., 1994; Yokoyama et al., 2002; Chen et al., 1999).

In East Asian countries, ~ 40% of the population carry a genetic variant in the aldehyde dehydrogenase 2 (ALDH2) enzyme that metabolizes acetaldehyde to acetic acid [10, 11]. … The ALDH2 genetic variant (ALDH2*2, rs671), causes acetaldehyde accumulation along with facial flushing and tachycardia after alcohol consumption [12]. … The ALDH2*2 variant leads to an accumulation of acetaldehyde after alcohol consumption which contributes to an overproduction of ROS leading to carcinogenesis [13, 14].

As described in this comic, the facial flushing that occurs after alcohol consumption is a warning sign that the body cannot break-down a metabolite of alcohol, called acetaldehyde. … Since alcohol is typically a beverage we drink, the alcohol exposure is concentrated within the digestive system – leading to higher risks of cancer particularly of the upper digestive track (mouth and esophagus) due to the limited ability to metabolize the alcohol metabolite acetaldehyde to acetic acid.

The frequency of this variant of ALDH2 (ALDH2 Glu504Lys) is low in caucasian, whereas the frequency is 30-50% in East Asian populations, especially in Chinese, Korean and Japanese (Goedde et al. 1992 ).

A functional variant in alcohol dehydrogenase 1B (ADH1B) is protective in people of European and Asian descent, and a different functional variant in the same gene is protective in those of African descent. A strongly protective variant in aldehyde dehydrogenase 2 (ALDH2) is essentially only found in Asians.

Alcohol metabolism occurs through a two-step process, whereby alcohol dehydrogenase (ADH) enzymes catalyze the conversion of alcohol to acetaldehyde and aldehyde dehydrogenase (ALDH) enzymes catalyze the subsequent conversion of acetaldehyde into acetate (Edenberg, 2007) . … The alleles are more prevalent among Asians than other racial/ethic groups, such as Europeans and African Americans (Wall et al., 2016) . Specifically, ALDH2*2 frequencies range from 0.11 to 0.28 among Asians while ALDH2*2 is virtually absent in other racial/ethnic groups (Wall et al., 2016) .

A functional variant in alcohol dehydrogenase 1B (ADH1B) is protective in people of European and Asian descent, and a different functional variant in the same gene is protective in those of African descent. … A strongly protective variant in aldehyde dehydrogenase 2 (ALDH2) is essentially only found in Asians. … The likely mechanism of protection against heavy drinking and AUDs in both cases is alteration in the rate of metabolism of EtOH that at least transiently elevates acetaldehyde.

Whilst pronounced alcohol flushing is rarely observed in Europeans, approximately 36% of East Asians experience alcohol flushing as well as other unpleasant symptoms (e.g. nausea and tachycardia) [1]. … These genes encode enzymes that metabolize alcohol into acetaldehyde (ADH1B) and acetaldehyde into acetate (ALDH2). Genetic variants in ALDH2 and ADH1B alter alcohol metabolism leading to prolonged, elevated levels of acetaldehyde.

The A allele of rs671 (a functional variant in the ALDH2 gene) was linked to higher levels of low-density lipoprotein cholesterol (LDL-C) and lower levels of triglycerides and high-density lipoprotein cholesterol. … In contrast, the A allele of the rs1229984 (a functional variant in the ADH2 gene) was associated only with lower levels of LDL-C.

Meta-analyses were conducted to determine the magnitude of relationships between polymorphisms in 2 genes, ALDH2 and ADH1B, with alcohol dependence in Asians. … For each gene, possession of 1 variant *2 allele was protective against alcohol dependence, and possession of a 2nd *2 allele did not offer significant additional protection.

Variants of three genes encoding alcohol-metabolizing enzymes, the aldehyde dehydrogenase gene ALDH2 and the alcohol dehydrogenase genes ADH1B and ADH1C, have been associated with reduced rates of alcohol dependence. The genotype prevalence of these genes varies in general samples of different Asian ethnic groups.

Many individuals of East Asian descent have a "superactive" form of ADH that speeds the conversion of alcohol (ethanol) to toxic acetaldehyde. … Another enzyme, called aldehyde dehydrogenase 2 (ALDH2), metabolizes toxic acetaldehyde to nontoxic substances. Some people, also particularly those of East Asian descent, have a form of this enzyme that causes acetaldehyde to build up when they drink alcohol.

There is also a high individual variability in ethanol metabolism, with alcohol elimination rates varying as much as three to four-fold among individuals (Li et al., 2001). Such an individual variability is mainly due to genetic vari ations in the main ethanol and acetaldehyde metabolizing en zymes.

Approximately, 30-40% of the Asian population have an inherited deficiency for aldehyde dehydrogenase 2, resulting in the accumulation of acetaldehyde.

The minor allele "A", also known as the ALDH2*2 allele, encodes a glutamate-to-lysine substitution at the position 487 of the mature protein (Glu487Lys), which effectively disrupts enzymatic activities (Online Mendelian Inheritance in Man (OMIM) #100650) and causes the accumulation of aldehydes in the human body [21].

About a third of people of East Asian descent have a genetic variant that leads to "Asian glow," a distinctive red flushing that appears after drinking alcohol. It's due to the body's inability to rid itself of acetaldehyde, a toxic byproduct of metabolizing alcohol.

The dysfunctional ALDH2 variant affects nearly 8% of the world population and is highly concentrated among East Asians.

East Asian populations, where alcohol consumption is rising, has a high prevalence of the inactivated aldehyde dehydrogenase-2 (ALDH2) enzyme involved in alcohol metabolism.

These three genes code for isoenzymes that metabolize alcohol into acetaldehyde (ADH1B and ADH1C) and acetaldehyde into acetate (ALDH2). … The variant forms of the alleles (ADH1B*2, ADH1C*1, and ALDH2*2) are hypothesized to alter conversion rates during alcohol metabolism and lead to an excess buildup of acetaldehyde (see Eriksson 2001).

Although it is known that variation in the aldehyde dehydrogenase 2 ( ALDH2 ) gene family influences the East Asian alcohol flushing response, knowledge about other genetic variants that affect flushing symptoms is limited.

The current meta-analysis tested independent and composite associations of three commonly studied alcohol metabolism alleles with alcohol use disorder (AUD) within East Asians as well as characterized potential moderating factors in these associations.