Causes[edit]
It is commonly thought that the flush reaction is caused by an inability to metabolize alcohol. To the contrary, around 80% of Asian people (less common in Thailand and India) have a variant of the gene coding for the enzyme alcohol dehydrogenase called ADH1B, and almost all Chinese and Korean people have a variant of the gene called ADH1C, [8] both resulting in an alcohol dehydrogenase enzyme that converts alcohol to toxic acetaldehyde at a much higher efficiency than other gene variants (40 to 100-fold in case of ADH1B).[2] In about 50% of Asians, the increased acetaldehyde accumulation is worsened by another gene variant, the mitochondrial ALDH2 allele, which results in a less functional acetaldehyde dehydrogenase enzyme, responsible for the breakdown of acetaldehyde.[8] The result is that affected people may be better at metabolizing alcohol, often not feeling the alcohol "buzz" to the same extent as others, but show far more acetaldehyde-based side effects while drinking.
\begin{smallmatrix}
&\text{H}& &\text{H}& & & &\text{H}& &\text{H}& & &\text{H}& & & \\
& | & & | & &\mathsf{ADH} & & | & & | &\mathsf{ALDH} & & | & & & \\
\text{H}\,-\!&\text{C}&\!-\!&\text{C}&\!-\,\text{O}\,-\,\text{H}&\xrightarrow{\qquad}&\text{H}\,-\!&\text{C}&\!-\!&\text{C}&\xrightarrow{\qquad\ }&\text{H}\,-\!&\text{C}&\!-\!&\text{C}&\!-\,\text{O}\,-\,\text{H}\\
& | & & | & & & & | & & \| & & & | & & \| & \\
&\text{H}& &\text{H}& & & &\text{H}& &\text{O}& & &\text{H}& &\text{O}& \\
\end{smallmatrix}
Metabolism of alcohol (ethanol) to acetaldehyde (ethanal) and then acetic acid (ethanoic acid)
Genetics[edit]
Alcohol flush reaction is best known as a condition that is experienced by people of Asian descent. According to the analysis by HapMap project, the rs671 allele of the ALDH2 gene responsible for the flush reaction is rare among Europeans and Africans, and it is very rare among Mexican-Americans. 30% to 50% of people of Chinese and Japanese ancestry have at least one ALDH2 allele.[9] The rs671 form of ALDH2, which accounts for most incidents of alcohol flush reaction worldwide, is native to East Asia and most common in southeastern China. It most likely originated among Han Chinese in central China,[10] and it appears to have been positively selected in the past. Another analysis correlates the rise and spread of rice cultivation in Southern China with the spread of the allele.[2] The reasons for this positive selection aren't known, but it's been hypothesized that elevated concentrations of acetaldehyde may have conferred protection against certain parasitic infections, such as Entamoeba histolytica.[11]
