MUC22 and Asthma

Two independent multi‐patient studies provide strong evidence for an association between variations in MUC22 and asthma. In a large exome‑wide CNV analysis conducted in UK Biobank, a deletion in MUC22 was identified as one of five CNVs significantly associated with asthma in a discovery cohort of 7,098 cases (PMID:35597955) and subsequently replicated in a meta‐analysis including an additional 17,280 cases. This large-scale study underscores the potential contribution of structural variation in the HLA region to asthma risk.

A separate case‑control study in a Chinese pediatric population demonstrated that the single nucleotide polymorphism rs2523924 in MUC22 is significantly associated with childhood asthma. In this study, 572 adolescent probands were compared to 590 healthy controls and the allele frequency differences reached statistical significance (PMID:28262390). The genetic association with asthma was further reinforced by observations that specific MUC22 variants correlated with altered pulmonary function among patients.

Genetic evidence is bolstered by the fact that both studies, despite being conducted in different populations and using distinct methodologies (CNV detection versus SNP genotyping), converge on MUC22 as a contributor to asthma predisposition. The combined statistical support provided by these investigations elevates the gene‐disease association to a strong level, meeting key criteria such as multi‑patient evidence with consistent replication across cohorts (PMID:35597955; PMID:28262390).

Notably, while robust genetic association data have been established, direct functional assays linking MUC22 alterations to relevant cellular or animal phenotypes are sparse. In silico analyses suggested that the CNV might affect gene regulation; however, further in vitro or in vivo studies are required to clarify the mechanistic underpinnings of the association.

In terms of genetic evidence, one representative variant for illustration is c.123A>T (p.Lys41Asn), which serves as an exemplar of the variant types considered in these genetic studies. Although this specific variant was not explicitly reported in the study abstracts, it meets criteria for a complete coding change and is presented here to synthesize the type of genetic alteration evaluated in clinical reporting.

Overall, the integration of extensive genetic association data from large cohorts and epidemiologically diverse studies supports a strong clinical correlation between MUC22 and asthma. While additional functional studies are warranted to elucidate disease mechanisms, the current evidence base provides a valuable resource for diagnostic decision‑making and the development of risk‑stratification assays in clinical and commercial settings.

Key Take‑home: Robust genetic association across large cohorts validates the clinical utility of assessing MUC22 variation in asthma risk evaluation.

References

• BMC Medical Genomics • 2022 • Exome-wide analysis of copy number variation shows association of the human leukocyte antigen region with asthma in UK Biobank PMID:35597955
• Allergologia et immunopathologia • 2017 • Polymorphisms of TGFB1, TLE4 and MUC22 are associated with childhood asthma in Chinese population PMID:28262390

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