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Library / trait / ADH1C — the slower sibling enzyme

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ADH1C — the slower sibling enzyme

ADH1Crs698metabolism
Trait
4 caveats1 population2 references

What this means

ADH1C is part of the alcohol dehydrogenase cluster on chromosome 4 — a family of enzymes that handle the first step of alcohol metabolism (ethanol → acetaldehyde). rs698 is the I350V coding variant: the A allele encodes the ADH1C*1 isoenzyme (Ile350), which is enzymatically faster, while the G allele encodes ADH1C*2 (Val350), which is slower. The effect on overall alcohol metabolism is much smaller than ADH1B rs1229984 — ADH1C contributes less to total activity — but the variant has been linked to modest differences in consumption and in alcohol-use disorder risk in multiple cohorts. ADH1B and ADH1C are in linkage disequilibrium, so reading either variant in isolation is incomplete.

ADH1C is one of a small family of enzymes your liver uses to start breaking down alcohol. There are two common versions of this enzyme: a faster one and a slower one. The difference between them is real but small — the effect on how quickly you actually process alcohol is much smaller than the well-known ADH1B "fast" change. Studies have linked the slower version to slightly higher average drinking in some groups, but the signal is modest. The cleanest way to think about ADH1C is as a supporting role: it adds detail to the alcohol- metabolism picture that ADH1B and ALDH2 paint.

Caveats

  • Effect size on alcohol metabolism is small compared with ADH1B rs1229984.
  • ADH1B and ADH1C are in strong linkage disequilibrium; reading either alone is incomplete.
  • The protective effect on alcohol-use disorder, where reported, is modest.
  • Allele frequencies vary substantially across ancestries.

Populations

  • Studied across European, East Asian, and African ancestries; allele frequencies vary

References