ACAA1 – Asthma

The association of ACAA1 with asthma has been evaluated in two independent multi‑patient studies that investigated innate immune gene polymorphisms in childhood respiratory diseases. These studies screened hundreds of single nucleotide polymorphisms (SNPs) in various innate immune genes in cohorts drawn from the Boston Home Allergens and Asthma Study and the Connecticut Childhood Asthma Study, providing a comprehensive assessment of genetic variation in asthma (PMID:22192168).

In one study, statistically significant associations were identified between several SNPs and asthma, with ACAA1 emerging as one of the candidate genes through its observed genetic signal. In particular, a significant interaction was detected between endotoxin exposure and a polymorphism in ACAA1 in a cohort of 372 children (PMID:22151743), suggesting that environmental factors may modulate the genetic risk conferred by ACAA1 variants.

The clinical validity of the association is rated as Moderate. While the data do not include traditional familial segregation, the statistically robust findings across independent cohorts and the documented gene‐environment interaction provide confidence in the contributory role of ACAA1 in the complex pathogenesis of asthma. This supports further investigation in larger cohorts and more refined phenotyping.

Genetic evidence for ACAA1’s role in asthma is bolstered by these case‑control and interaction studies. Although the variant details are derived from analyses of common polymorphisms without detailed functional characterization in an asthma context, the cumulative evidence from significant p‑values and replication across studies underscores a moderate level of genetic evidence. A representative variant from ACAA1, identified in other assessments, is noted as c.89>C (p.Asn299Ser) even though its primary functional evaluation was in a different disease context.

Functional evidence specific to asthma remains limited. Available in vitro and in vivo studies on ACAA1 have primarily been performed in the context of Alzheimer disease, leaving a gap in direct experimental confirmation of ACAA1’s role in asthma pathobiology. Accordingly, while genetic evidence supports the association, the mechanistic underpinnings for asthma await further functional exploration.

In summary, the integration of robust association signals, significant gene–environment interactions, and replicated findings across independent cohorts provides a coherent narrative for a moderate level of gene–disease association between ACAA1 and asthma. This evidence, although not complete in functional validation for asthma, is sufficient to support diagnostic decision‑making, guide commercial assay development and warrants further study in future publications.

References

• Pediatric Allergy and Immunology • 2012 • Association of variants in innate immune genes with asthma and eczema PMID:22192168
• BMC Medical Genetics • 2011 • Effects of endotoxin exposure on childhood asthma risk are modified by a genetic polymorphism in ACAA1 PMID:22151743

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