Alcohol-Related Proteomic Signatures Vary by Drinking Pattern

Researchers analyzed plasma proteomic data from 47,514 UK Biobank participants to characterize protein responses across drinking patterns defined by intake level, dominant beverage type and sex. They identified 12 pattern-specific signatures and assessed linear and nonlinear associations with gastrointestinal disease risks. Shared proteins were also evaluated in an independent cohort and in mice exposed to graded ethanol.

Alcohol drinking was associated with 475 plasma proteins, with enrichment in immune, inflammatory, adhesion and lipid-related pathways. Signatures differed across drinking patterns, and their associations with gastrointestinal outcomes were heterogeneous and nonlinear. Among people with similar reported intake, beverage- and sex-specific signatures showed distinct risk curves. APOM, MAMDC4 and SERPINA7 were retained across patterns, correlated with alcohol intake and distinguished regular from occasional drinkers better than conventional liver enzymes in the analyses; these findings were validated in the additional cohort and mouse model.

The results suggest that proteomic responses may capture biological variation not reflected by reported alcohol volume alone. However, this observational work does not show that the signatures improve clinical risk prediction or patient outcomes, and the proteins are not established clinical tests. The findings do not support changing alcohol assessment or gastrointestinal care on their own.