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This summary outlines the association between RNASE3, a gene encoding eosinophil cationic protein, and asthma. Multiple independent studies have evaluated the impact of RNASE3 variants on allergic asthma phenotypes and related biomarkers. The clinical investigations incorporate both population-based family studies and functional assays that support an etiologic role for RNASE3 in allergic airway inflammation. The evidence is derived from rigorous genetic studies using transmission disequilibrium tests and replication in meta-analyses. These studies provide robust statistical associations that underline RNASE3 as an important susceptibility locus for asthma. Overall, the data is essential for diagnostic decision‑making and commercial considerations.
The clinical validity of the RNASE3–asthma association is supported by strong evidence. Family‐based studies, including one analyzing 177 families (PMID:17362255), have identified significant haplotype associations with allergic asthma. A subsequent meta‑analysis in 1018 subjects (PMID:35671886) reinforced these observations by linking specific RNASE3 haplotypes to increased s‑ECP levels and other asthma‐related traits. Such replicated findings across independent cohorts have led to a strong overall association categorization. The evidence is bolstered by underlying statistical rigor and comprehensive phenotypic assessments. This information is of substantial relevance for future publication and clinical applications.
Genetic evidence indicates that the inheritance pattern is consistent with an autosomal dominant effect in the context of complex traits. Although asthma is a multifactorial disorder, the genetic analyses focused on RNASE3 highlight significant associations within family cohorts. Segregation analysis did not report a high number of additional affected relatives, with affected relatives counted as 0 in the available data. The variant spectrum includes single‐nucleotide changes, with one key variant, c.434G>C (p.Arg97Thr), being implicated. This variant appears to significantly alter the protein’s function in immune modulation. The delineation of the variant's impact enhances its relevance in assessing disease susceptibility.
Functional assessments have provided moderate yet compelling support for the pathogenic role of RNASE3 variations in asthma. In vitro studies demonstrated that the coding polymorphism c.434G>C (p.Arg97Thr) dramatically alters the cytotoxic function of ECP (PMID:19542456). Further structural and biochemical studies confirmed that alterations in RNASE3 also affect its binding properties to heparin (PMID:24349317). These experimental results are concordant with the hypothesis that altered protein function may affect airway inflammation and remodeling in asthma. Cellular models and binding assays provide a mechanistic bridge between the genetic association and the observed clinical phenotypes. Such mechanistic evidence is vital in correlating genotype with phenotype.
There is no significant conflicting evidence reported that disputes the association between RNASE3 and asthma. Some studies assessing related allergic phenotypes in the same cohorts reaffirm the association, although they also implicate additional genes in the broader inflammatory network. The consistency between genetic and experimental data underscores a clear link between RNASE3 variants and asthma susceptibility. While polygenic factors contribute to the disease, the evidence for RNASE3 is not diluted by confounding studies. Any alternative findings have not reached a level to challenge the current clinical interpretation. This consolidated view supports the clinical robustness of the association.
In conclusion, the integration of genetic and functional evidence underpins a strong association between RNASE3 and allergic asthma. Cumulative data from family-based association studies and functional assays provide a reliable foundation for both diagnostics and therapeutic strategies. The variant c.434G>C (p.Arg97Thr) serves as a representative marker for this association, with compelling evidence from multiple independent cohorts and in vitro studies. The clinical utility of assessing RNASE3 in the context of asthma is evident from its reproducible genetic signals and mechanistic insights. This relationship is instrumental in refining risk stratification and may guide future personalized interventions. Key take‑home: RNASE3 is a clinically significant contributor to allergic asthma, supporting its integration into diagnostic panels and future research initiatives.
Gene–Disease AssociationStrongGenetic associations observed in independent family-based studies, with significant TDT results in 177 families (PMID:17362255) and replication in meta-analysis of 1018 subjects (PMID:35671886). Genetic EvidenceStrongHaplotype analyses and genome-wide associations in multiple cohorts support the involvement of RNASE3 variants in allergic asthma, with robust statistical signals and evidence from diverse populations. Functional EvidenceModerateIn vitro assays demonstrate that the RNASE3 c.434G>C (p.Arg97Thr) polymorphism alters cytotoxic activity (PMID:19542456) and affects heparin binding properties (PMID:24349317), consistent with the observed phenotype. |