In Chinese, and other East Asian populations, two common genetic variants (alleles) reduce alcohol tolerability and are strongly associated with lower alcohol intake, because they cause an unpleasant “flushing” effect. These mutations both disrupt the functioning of enzymes involved in alcohol detoxification, causing the toxic compound acetaldehyde, a Group I carcinogen, to accumulate in the blood.
The first mutation is a loss-of-function mutation in the gene for the enzyme aldehyde dehydrogenase 2 (ALDH2). The second mutation accelerates the activity of alcohol dehydrogenase 1B (ADH1B). Both are common in East Asians but rare in European ancestry populations.
Because these alleles are allocated at birth and are independent of other lifestyle factors (such as smoking), they can be used as a proxy for alcohol intake, to assess how alcohol consumption affects disease risks.
The study team used DNA samples from approximately 150,000 participants (roughly 60,000 men and 90,000 women) in the China Kadoorie Biobank study and measured the frequency of the low-alcohol tolerability alleles for ALDH2 and ADH1B.
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