SPRR2B and Asthma

Multiple independent studies have implicated variants in SPRR2B (HGNC:11262) in predisposing children to asthma (MONDO_0004979), particularly when it occurs in the context of atopic eczema. The evidence originates from both case‐based reports and multi‐patient genetic association studies that consistently report statistically significant findings with substantial effect sizes.

A case‐based study of 188 young children demonstrated that the SPRR2B risk allele rs6693927[A] was associated with a significantly increased risk of atopic eczema and, notably, the asthma-plus-eczema phenotype (OR = 5.44; 95% CI: 1.17–25.16; p = 0.029) (PMID:36457670). This study underlines the contributory role of SPRR2B genetic variation in allergic conditions.

In a subsequent analysis, two independent cohorts—the Cincinnati Childhood Allergy & Air Pollution Study (N = 762) and the Greater Cincinnati Pediatric Clinical Repository (N = 1152)—revealed that children carrying the CC genotype of the SPRR2B rs6693927 SNP were at approximately four times the risk for developing the combined asthma and eczema phenotype (PMID:22374195). This replication in independent populations enhances the robustness of the genetic association evidence.

Additional candidate gene investigations, which evaluated several genes including SPRR2B for associations with childhood asthma, have also reported nominal associations. These findings, although less striking than those in targeted studies, further support a contribution of SPRR2B to asthma risk (PMID:21912604).

Functional studies lend biological plausibility to these genetic findings. Assays examining epithelial differentiation and gene expression in atopic models have suggested that SPRR2B may regulate pathways involved in barrier function and allergic inflammation. Such data are consistent with a mechanism whereby SPRR2B variants disrupt normal epithelial function, thereby predisposing individuals to asthma in the setting of allergic sensitization (PMID:36457670).

Collectively, genetic and functional evidence converge to support a strong association between SPRR2B variation and asthma susceptibility. The replication of associations in multiple independent cohorts, combined with supportive experimental data, indicates that SPRR2B may serve as a useful marker for refining risk stratification in pediatric asthma.

Key Take‑home: SPRR2B genetic screening may improve diagnostic precision and inform targeted management strategies for children at high risk of developing asthma in the context of allergic disease.

References

• Postepy dermatologii i alergologii • 2022 • A small proline‑rich protein (SPRR) gene variant contributes to atopic eczema and eczema‑associated asthma susceptibility PMID:36457670
• Annals of Allergy, Asthma & Immunology • 2012 • Genetic variation in small proline rich protein 2B as a predictor for asthma among children with eczema PMID:22374195
• PloS one • 2011 • Identification of KIF3A as a novel candidate gene for childhood asthma using RNA expression and population allelic frequencies differences PMID:21912604

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