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The following is a summary of “Genetically Determined Inflammation-Related Proteins in Asthma and Type-2 Signatures,” published in the June 2025 issue of European Journal of Allergy and Clinical Immunology by Hernandez-Pacheco et al. 

Protein quantitative trait loci (pQTLs) remained underexplored in asthma but offered potential insights into its underlying molecular mechanisms.  

Researchers conducted a retrospective study to examine associations between genetic variation and inflammation-related plasma proteins and to evaluate differences in genetically influenced protein levels among individuals with type 2 inflammation and/or asthma.  

They performed pQTL mapping of 92 inflammation-related plasma proteins in young adults from the Swedish BAMSE (Barn, Allergy, Milieu, Stockholm, and Epidemiology) cohort (n=1538). Replication of sentinel pQTLs was attempted, and their overlap and colocalization with expression quantitative trait loci (eQTLs) were analyzed using publicly available datasets. Proteins with significant pQTLs were then tested for associations with type 2 inflammation signatures, defined by elevated fractional exhaled nitric oxide, increased blood eosinophils, and/or sensitization to airborne allergens in individuals with or without asthma.  

The results showed that 45 sentinel pQTLs, including 33 cis and 12 trans variants, were identified for 39 inflammation-related proteins (P≤ 7.14 × 10^-11). A large proportion of these pQTLs were confirmed in independent cohorts. Colocalization analysis revealed a strong overlap between cis-pQTLs and cis-eQTLs for 19 proteins across multiple tissues. Among the 39 proteins with significant pQTLs, 6 were linked to type 2 inflammation signatures and/or asthma. Matrix metalloproteinase-10 (MMP-10) demonstrated the strongest associations.  

Investigators concluded that genetic factors influenced plasma levels of inflammation-related proteins, including MMP-10, which appeared to contribute to elevated type 2 inflammation in individuals with asthma, highlighting its relevance to pulmonology. 

Source: onlinelibrary.wiley.com/doi/10.1111/all.16608