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Genetic variants regulate circulating inflammatory proteins, with MMP-10 showing the strongest link to type-2 inflammation and asthma.
A large-scale Swedish study issued in "Allergy" has revealed how genetic variation shapes the levels of inflammation-related proteins in the blood, providing novel biological insights into asthma and type-2 inflammatory pathways.
Researchers from the BAMSE birth cohort analyzed 92 plasma proteins implicated in inflammation in 1,538 young adults using protein quantitative trait loci (pQTL) mapping. Their investigation identified 45 sentinel pQTLs (33 cis and 12 trans) that influenced 39 distinct proteins with high statistical significance (p ≤ 7.14 × 10⁻11). A substantial number of these connections were successfully replicated in independent datasets, strengthening the validity of the findings.
To better comprehend the regulatory context, the team examined the overlap between pQTLs and expression quantitative trait loci using publicly available data. They found a high likelihood of colocalization for 19 proteins across multiple tissues, indicating that the same genetic variants often influence both gene expression and protein levels. The clinical relevance of these proteins was further explored by testing their connection with asthma and type-2 inflammation signatures, including high fractional exhaled nitric oxide, elevated blood eosinophil counts, and sensitization to airborne allergens.
Notably, 6 of the 39 proteins with significant pQTLs were linked to these disease signatures. Among them, matrix metalloproteinase-10 (MMP-10) showed the strongest and most consistent association, suggesting it could play a central role in the heightened airway inflammation seen in asthma patients with strong type-2 immune responses. According to the authors, the findings highlight that genetic variation is a key driver of circulating inflammatory protein levels. This knowledge could advance the search for biomarkers and therapeutic targets in asthma, particularly in those with type-2 inflammation, where current treatment options remain limited.
Allergy
Genetically Determined Inflammation-Related Proteins in Asthma and Type-2 Signatures
Natalia Hernandez-Pacheco et al.
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