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SPRR2B has emerged as an important risk factor for atopic eczema, with multiple independent studies demonstrating that carriers of the risk allele have a significantly increased chance of developing the disease and the eczema‐associated asthma phenotype. In these studies, the risk allele (rs6693927[A]) was consistently associated with odds ratios ranging from 3.02 to 5.44, and the association remained significant independent of FLG mutations (PMID:36457670, PMID:22374195). The evidence comes from both case reports and multi‐patient studies, reinforcing the reliability of the reported association.
The overall clinical validity of the SPRR2B–atopic eczema association is classified as Strong. This judgment is supported by replication in independent cohorts that included 188 probands (PMID:36457670) and corroborative findings in additional studies (PMID:22374195). Although detailed family segregation data were not provided, the repeated statistical significance across diverse populations lends robustness to the association.
Genetic evidence is robust, with the risk allele being investigated in both single‐center case reports and larger, independent multi‐patient cohorts. In one study, 188 children were analyzed and the risk allele showed a significant association with atopic eczema, with additional studies confirming a similar trend when considering the combined eczema‐plus‐asthma phenotype. This evidence underscores a multifactorial, complex inheritance pattern rather than a classic Mendelian mode.
Functional evidence, while not extensive, suggests that the SPRR2B variant may impact epidermal differentiation and barrier function. Although the experimental assays have been limited to association‐type studies rather than detailed mechanistic investigations, these findings support a biological role that is concordant with the clinical phenotype of atopic eczema. Such limited functional data add a layer of biological plausibility to the genetic observations.
Integration of the genetic and functional data provides a coherent narrative: the SPRR2B risk allele significantly elevates the risk for atopic eczema and its associated asthma phenotype. The convergent evidence from replicated association studies and supportive, though limited, functional assessments justifies its strong clinical validity. This cumulative evidence not only advances our understanding of disease pathogenicity but also emphasizes the utility of incorporating SPRR2B status into diagnostic and predictive models.
Key take‑home sentence: The SPRR2B risk allele represents a robust genetic marker for atopic eczema, offering valuable insights for diagnostic decision‑making and potential commercial applications.
Gene–Disease AssociationStrongEvidence from independent cohorts including 188 probands (PMID:36457670) with replication in additional studies (PMID:22374195) supports a strong gene‐disease association. Genetic EvidenceStrongMultiple studies demonstrated significant associations with the rs6693927 risk allele, confirming its role in atopic eczema through consistent odds ratios and repeated validations. Functional EvidenceLimitedAlthough experimental assessments of SPRR2B’s function are sparse, available data suggest potential impacts on epidermal barrier integrity, aligning with the clinical phenotype. |